Arthritis_Summary_Notes

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University of New South Wales *

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Medicine

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Oct 30, 2023

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Nicodemus Tedla_2023 1 Revision notes on Arthritis Definitions: • Arthralgia : pain of any cause in a joint or joints • Arthritis : inflammation of a joint or joints characterized by pain, swelling and redness What are the main causes of arthritis? 1. Recurrent Inflammatory type of arthritis o Rheumatoid arthritis : symmetrical poly arthritis of small joint (synovitis) o Psoriatic arthritis : asymmetric oligoarthritic of the distal interphalangeal and nails o Spondyloarthropathies : Mostly associated with HLA-B27; synovitis. ▪ Ankylosing spondylitis ▪ R eiter’s syndrome (r eactive arthritis) ▪ Inflammatory bowel disease o Connective tissue diseases : rare ▪ SLE ▪ Systemic vasculitis o Crystal-induced arthritis ▪ Gout: uric acid deposition ▪ Pseudogout: calcium pyrophosphate deposition o Juvenile idiopathic arthritis 2. Degenerative joint disease o Osteoarthritis, spondylitis ▪ Primary OA: Age related wear and tear ▪ Secondary OA: joint damage due abnormal forces or mechanical stress (obesity) 3. Arthritis that are associated with infection. o Bacterial ▪ Acute septic or suppurative arthritis (gram negative rods) • Gonococcal: in patients with complement deficiency • Staphylococcus: post trauma, IV drug users, AIDS patients • Salmonella: in patients with sickle cell anemia ▪ Chronic bacterial arthritis • TB • Lyme disease o Viral: Hepatitis B and C, Ross River, Rubella etc o Reactive: Gonococcal, meningococcal , Streptococcus, H. influenza and Reiter’s syndrome

Nicodemus Tedla_2023 2 Rheumatoid arthritis How do you define RA? • Systemic chronic recurrent inflammation of multiple tissue but principally attacking joints. • It mainly affects small joints symmetrically producing non-suppurative, proliferative synovitis that frequently progresses to destroy articular cartilage and underlying bone leading to a debilitating disease. What is the etiology of RA? • Etiology is unknown; may be an autoimmune disease triggered by some infectious agents (EBV, mycoplasma, Borrelia spps, parvovirus) in genetically predisposed individuals. • There is some genetic predisposition (increased frequency in some families and twins, linked to certain MHC molecules such as HLADR1/4) • Affects women 3-5X more than men and is common in the age group between 20-40 yrs • Affects 1% of the general population. What is the immunopathogenesis of RA? Produce MMPs APC presents antigen to CD4 cells via MHC II CD4 cells produce cytokines that activate. Osteoclasts B cells to produce IgM against Fc portion of self-IgG Immune complex formation Joint injury Recruitment of PMN Pannus formation Joint destruction Macrophages Endothelial cells Produce cytokines and growth factors Proliferation of chondrocytes, fibroblasts and synovsitis Increased adhesion Increased inflammatory cell infiltration. Increased angiogenesis

Nicodemus Tedla_2023 3 Which joints are affected in RA? • Symmetrical arthritis affecting small joints of the hand and feet, knee, ankle, wrist, elbow and shoulder. • Classically PIP and MCP joins are affected but not DIP (xOA Heberden ‘s nodules) • Vertebral and hip involvement are extremely rare (xOA) What are the pathological changes in RA? • Macroscopic: o Red, painful, fusiform swelling of PIP joints leading to stiffness and ankyloses. o Erosion of articular cartilage, osteopenia of the underlying bone o Severe damage of tendons, ligaments and joint capsule leading to deformities ▪ Radial deviation of wrist ▪ Ulnar deviation of fingers ▪ Flexion hyperextension of fingers (Swan neck, Boutonniere) o Subcutaneous nodules (1/4 th of pts), 1-2 cms; firm non-tender oval mass ▪ Extensor surface of the forearm ▪ Other areas are subjected to mechanical pressure. ▪ Rarely in the heart, lung, spleen and the aorta • Microscopic: o Chronic synovitis characterized by ▪ Hyperplasia and hypertrophy of the synovial cells ▪ Perivascular infiltration of inflammatory cells sometimes forming lymphoid follicles with CD4 cells, Mac and plasma cells ▪ Formation of granulation tissue with new blood vessels and fibroblast proliferation, edematous swelling ▪ Aggregation of neutrophils and fibrin in the joint cavity and synovial surface ▪ Increased osteoclastic activity leads to erosion of the underlying bone. o Invasive Pannus: proliferating synovial lining cells admixed with inflammatory cells, fibrin and granulation tissue whereby: ▪ The thin synovial membrane is transformed to thick, lush edematous villous proliferation. ▪ Articular cartilage subjacent to the pannus is destroyed and the underlying bone is eroded. o Finally, pannus fills the joint space with fibrosis and calcification leading to permanent ankylosis. o Subcutaneous nodules: central necrosis surrounded by macrophages and granulation tissue. What are the clinical features of RA? • Symmetrical polyarthritis

Nicodemus Tedla_2023 4 • Insidious aching and stiffness of joints (morning) • Progressive swelling, limitation of movement, deformity and ankylosis • Weakness, malaise, low grade fever and weight loss What are complications of RA? (Reduces life expectancy by 3-7 years) • Articular complications (Pannus invasion) o Deformity o Fibrosis o Permanent ankylosis o Limitation of movement, loss of movement • Extra articular complications o Anemia of chronic disease (normochromic, normocytic) o Wt loss (TNF  , IL-1) o Immune complex mediated hypersensitivity. ▪ Vasculitis syndromes (acute necrotizing vasculitis) • Nail fold infraction • Angina, myocarditis • Raynaud’s phenomena and leg ulcer • Rheumatoid arteritis ▪ Serosal involvement (pleurisy, pericarditis) ▪ Uveitis and kerato-conjunctivitis ▪ Subcutaneous nodules o Hepatosplenomegaly and leukopenia (Felty’s syndrome) o Reactive amyloidosis (5-10%) Investigations • X-ray: o Joint effusion o Juxta articular Osteopenia o Narrowing of joint space o Loss of articular cartilage • FBC: o Anemia o Leukocytosis (PMN), lymphocytopenia, thrombocytosis o ER, CRP, Serum ferritin. • Serology: o RF (80%) (old age, SLE, Chronic liver disease, Endocarditis, Sjogren’s)

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