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142 Cards in this Set
- Front
- Back
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Two main types of joints
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Solid (non-synovial: synarthroses); cavitated (synovial)
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Two types of synarthroses
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Fibrous synarthroses: cranial sutures, teeth/jaw; Cartilaginous Synarthroses: symphyses (manubriosternalis and pubic)
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Synovial Fluid made up of:
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clear, viscous, plasma filtrate containing hyaluronic acid (for lubrication and nutrition)
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Hyaline Cartilage made up of:
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Type II collagen, water, proteoglycans, chondrocytes
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Function of water and proteoglycans in hyaline cartilage
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turgor and elasticity, important in limiting friction
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Chondrocyte function in hyaline cartilage
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synthesize and enzymatically digest matrix
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which cytokines trigger hyaline cartilage degradation?
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IL-1 and TNF
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Osteoarthritis characterized by:
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progressive erosion of articular cartilage, intrinsic disease of cartilage
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How does primary osteoarthritis initially appear?
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insidously, without apparent initiating cause, as aging process (idiopathic of primary osteoarthritis)
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What can cause secondary osteoarthritis?
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macrotrauma, repeated microtrauma (also obesity), congenity deformity in joint, underlying system disease (diabetes, ochronosis, Wilson's disease, hemochromatosis)
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Functions of normal articular cartilage (2)
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friction-less motion, spreads load across joint surface in weight-bearing joints
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Function of collagen II and proteoglycans in cartilage
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provide elasticity and high tensile strength
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evidence for role of aging and mechanical wear in osteoarthritis
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increasing occurrence with age, occurrence in weight-bearing joints, increase in freq of dz in joints exposed to abnormal stresses (obesity, previous joint deformity)
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Three major influences in osteoarthritis development
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aging, mechanical stress, genetic factors
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Cartilage changes in OA
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increased water, decreased proteoglycans, weakening of collagen network (decreased collagen II production, increased breakdown), levels of IL1, TNF, NO increased, apoptosis increased
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Typical age of onset of primary OA
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50's and up
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Characteristic symptoms of OA
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deep achy pain worsening with use, morning stiffness, crepitus, limited range of movement, one or few joints involved
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What are osteophytes?
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bony outgrowths
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Role of osteophytes in OA:
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impinge on spinal foramina, cervical/lumbar nerve root compression
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Which joints are involved in OA?
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hips, knees, lower lumbar/cervical vertebrae, proximal/distal IP joints, first carpometacarpal and first tarsometatarsal
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Heberden nodes
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characteristic of OA in women, nodes on fingers representing prominent osteophytes
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define ankylosis
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stiffening or fixation of a joint due to a disease process, with fibrous or bony union across joint
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RA progression
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1) infiltration of synovium by CD4+ and B cells, 2) increased vascularity, 3) fibrin aggregation, 4) neutrophil accumulation, 5) osteoclastic activity, 6) pannus formation, destroyed cartilage, ankylosis
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Skin nodules in RA
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arise in regions of skin that are subjected to pressure, less commonly in viscera, firm, nontender, round to oval, in SubQ
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Define Pannus
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mass of synovium and synovial stroma consisting of inflammatory cells, granulation tissue, and fibroblasts
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Which cells are involved in RA?
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CD4+ T cells and B cells
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What function to CD4+ Tcells play in RA?
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RANKL and stimulate other cells in joint to produce cytokines that are mediators of synovial reaction
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in RA, cytokines lead to:
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synovial cell production of mediators of inflammation and matrix metalloproteases
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What does RANKL do?
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activates osteoclasts and promotes bone destruction
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Which cells express RANKL?
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T-cells and synovial fibroblasts
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Which gene is linked to RA susceptibility?
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HLA-DR4 at Class II HLA locus
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Initial symptoms of RA:
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malaise, fatigue, generalized musculoskeletal pain
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Pattern of Joint Involvement in RA:
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small joints affected before larger ones (generally)
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Which joints involved in RA (specifically)?
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MCP, PIP, MTP, followed by wrists, ankles, elbows, knees
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Describe RA joints (externally)
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swollen, warm, painful, stiff on arising or after inactivity
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radiographic hallmarks of RA
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juxta-articular osteopenia and bone erosions with narrowing of joint space
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RA hand deformities (4)
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radial wrist deviation, ulnar finger deviation, swan neck fingers, boutonniere fingers
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boutonniere deformity
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MCP extension, PIP flexion, DIP extension
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swan neck deformity
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PIP hyperextension, DIP flexion
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RA if 4 of 7 following criteria for 6+ months
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1) morning stiffness, 2) arthritis in 3 or more joints, 3) arthritis of typical hand joints, 4) symmetric arthritis, 5) rheumatoid nodules, 6) serum rheumatoid factor, 7) typical radiographic changes
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3 subclasses of Juvenile Rheumatoid Arthritis
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oligarticular, polyarticular, systemic
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How long is a juvenile arthritis present before JRA is diagnosed?
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at least 6 weeks
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Five ways JRA differs from RA in clinical presentation
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in JRA, 1) oligoarthritis more common, 2) systemic onset more frequent, 3) large joints affected more often than small, 4) rheumatoid nodules and factor usually absent, 5) anti-ANA+ common
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Presentation of systemic JRA
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can be abrupt, migratory/transient skin rash, hepatosplenomegaly, serositis
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Presentation of seronegative spondyloarthropathies
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inflammatory peripheral/axial arthritis, tendon inflammation
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list the seronegative spondyloarthropathies (4)
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ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated w/ IBD
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what is ankylosing spondyloarthritis?
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chronic inflammatory joint disease of axial joints (esp. sacroiliac joints)
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when does ankylosing spondyloarthritis become symptomatic?
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2nd/3rd decades
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ankylosing spondyloarthritis disease progression
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tendinoligamentous insertion site inflammation, ossification, bony outgrowths, ankylosis, spinal immobility
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Definition of reactive arthritis
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episode of non-infectious arthritis of the appendicular skeleton that occurs within one month of primary infection localized elsewhere in the body
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Reiter Syndrome
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triad of arthritis, nongonococcal urethritis/cervicitis, conjuctivitis
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time course of reactive arthritis symptoms
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sx develop weeks after urethritis or diarrhea, joint stiffness and low back pain are early sx, wax and wane over weeks to months
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Who gets Psoriatic arthritis?
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10% of patients with psoriasis
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pattern of joint involvement in psoriatic arthritis?
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very diverse
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4 types of infectious arthritis
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suppurative, tuberculous, lyme, viral
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most common organisms causing acute suppurative arthritis
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gonoccocus, staph, strep, h. flu, GNR
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classic presentation of suppurative arthritis
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sudden development of acutely painful, hot, swollen joint, restricted range of motion, fever, leukocytosis, elevated ESR
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What does tuberculous arthritis accompany?
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complication of osteomyelitis or hematogenous dissemination from visceral site of infection
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pattern of joint involvement in tuberculous arthritis
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weight bearing joints
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pathogenesis of lyme arthritis
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borrelia burgdorferi seeds in joints within days/weeks of primary infection
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pattern of joint involvement in lyme arthritis
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big joints
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which viruses can cause viral arthritis?
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parvovirus b19, rubella, HepC
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3 crystals that can cause gout
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urate, calcium pyrophosphate dihydrate, calcium phosphate (hydroxyapatite)
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Gout pathogenesis
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hyperuricemia, transient attacks of acute arthritis, chronic gouty arthritis, creation of tophi
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what are Tophi?
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large aggregates of urate crystals and the surrounding inflammatory reaction
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2 causes of primary gout
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overproduction with normal excretion, normal production with under excretion
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3 causes of secondary gout
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leukemias (overproduction of uric acid), chronic renal disease (reduced excretion), inborn error of metabolism (HGPRT deficiency)
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Lesch-Nyhan Syndrome cause
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x-linked complete lack of hypoxanthine guanine phosphoribosyl transferase (HGPRT)
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Lesch-Nyhan Syndrome presentation
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severe mental retardation, self mutilation, gouty arthritis
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effect of age on Gout
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rarely appears before 20-30 years of hyperuricemia
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predisposing factors to gout
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increased age, genetic predisposition, heavy alcohol consumption, obesity, certain drugs, lead toxicity
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why gout in joints?
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synovial fluid is a poorer solvent for monosodium ureate than plasma, so it preferentially precipitates there
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what if acute gout untreated?
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resolves in hours to weeks, complete resolution leads to asymptomatic intercritical period, recurs, with each time, next recurrence sooner
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which age group gets pseudogout (CPPD)
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over 50, gets up to 30-60% in 85+
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crystal in pseudogout
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CPPD - calcium pyrophosphate deposition disease
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SLE affects more men or women?
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9:1 women, esp during childbearing years
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essential failure in lupus?
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failure of mechanisms that maintain self-tolerance
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4 categories of lupus ANAs
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anti-DNA, anti-histone, anti-RNA bound proteins, anti-nucleolar antigens
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Clinical lupus diagnosis?
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indirect immunofluorescence that detects generic ANAs
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which antibodies are diagnostic of SLE (2)?
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anti-dsDNA and anti-Sm
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Why do lupus patients potentially get syphilis false positives?
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make anti-phospholipd (phospholipid-beta2-glycoprotein complex), which cross reacts with cardiolipin, which is the target Ag in indirect treponemal testing
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explain Lupus Anticoagulant
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SLE ab that interferes w/ in vitro clotting tests, but the patients suffer from a hypercoagulable state
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Monoarticular Rheumatologic Diseases (3)
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Gout, Infection, Reactive
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Polyarticular Rheum Diseases (2)
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RA, SLE
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MTP Joint Distribution
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Gout
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DIP Joint Distribution
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Osteoarthritis, Psoriatic
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Which two diseases present with PIP/MCP Joint Distribution
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RA, SLE
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Symmetrical Rheum Diseases (2)
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RA, SLE
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Asymmetrical Rheum Diseases (2)
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Psoriatic, Reactive
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RA peak onset for women
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30's to 40's
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RA peak onset for men
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50's to 70's
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Which gene predisposes to RA?
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HLA-DR4
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RA disease development
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genetic predisposition + environmental trigger = preclinical autoimmunity = RA
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What is the major cell type found in synovial effusions?
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neutrophils
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Which type of T-cells found in joint?
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Th1, abundant
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Role of B-Cells in RA
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unknown, but depleting B-cells improves clinical dz activity
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Major pro-inflammatory cytokines in synovium (3)
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TNF-alpha, IL-1, IL-6
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Common extra-articular manifestations in RA (8)
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rheumatoid nodules, sjogren syndrome, interstitial lung disease, scleritis, pleuritis/pericarditis, vasculitis, felty syndrome
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Define Sjogren syndrome
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autoimmune disease of lacrimal glands and parotids, leading to dry eyes and dry mouth
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Lab findings in RA
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mild/moderate anemia, high ESR, elevated CRP, high neutrophils in synovial fluid
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Autoantibodies for RA diagnosis
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Rheumatoid factor, anti-CCP (cyclic citrullinated peptides)
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What is Rheumatoid Factor?
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Auto antibody against Fc of IgG; not sensitive of specific for RA
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Which of the two RA auto-antibodies are specific to RA?
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anti-CCP
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Differential Dx for RA
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viral infections (parvovirus B19, HepB), SLE, Spondyloarthropathies, OA
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RA Treatment
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NSAIDs, glucocorticoids, DMARDs, Biologicals
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NSAIDs in RA
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modest symptomatic relief, but don’t prevent joint destruction, NOT GOOD FOR MONOTHERAPY
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Glucocorticoids in RA
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low dose, improve sx, slow dz progression, use in conjunction w/ other drugs
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DMARDs in RA
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slow acting (weeks to months), slow dz progression
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examples of DMARDs
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methotrexate, leflunomide, sulfasalazine, hydroxychloroquine
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examples of Biologicals
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anti-TNF: adalimumab, infliximab, etanercept; IL1 antagonist: Anakinra
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Ddx for OA
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psoriatic arthritis, pseudogout, neuropathic (charcot) joint, trauma
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in OA, chemical shift in cartilage
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less keratan sulfate and more chondroitin 4-sulfate
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OA on xray
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non-uniform joint space narrowing, osteophytes, subchondrial bony sclerosis, occasional bone cysts
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OA treatment
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px education, exercise, mescle strengthening and joint protection, NSAIDs, steroid injections
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Causes of hyperuricemia (6)
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overproduction, increased purine biosynthesis, increased ATP breakdown, decreased renal clearance, intrinsic renal disease, competition for excretion by organic acids
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Gout pathogenesis
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phagocytosis of Ig coated crystals by synovial PMNs, induce cytokine release
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How to diagnose gout
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aspirate synovial fluid, look for needle like birefringent crystals
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Gout Treatment
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don’t treat asymptomatic hyperuricemia; use NSAIDs/corticosteroids for acute attack, low doce colchicine for chronic
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Pseudogout Clinical features
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acute, inflammatory, gout like secondary to CPPD crystals, older px, trauma common trigger, knee is main site, + birefringent crystals
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CPPD?
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calcium pyrophosphate dihydrate (causes pseudogout)
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pseudogout treatment
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NSAIDs, low dows colchicine
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Birefringent crystals
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positive if: blue when parallel, yellow when perpindicular
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five shared features of spondylarthropathies
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axial skeleton involvement, asymmetric peripheral joint arthritis, enthesitis, seronegativity, HLA-B27 association
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Genetic predisposition for spondylarthropathies
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HLA-B27
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is ankylosing spondy peripheral or axial?
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axial
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What establishes ankylosing spondy radiographically?
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bilateral, symmetrical sacroiliitis
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major extrauricular manifestation of ankylosing spondy?
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anterior uveitis (ocular pain, photophobia) --> claucoma and posterior synechiae; GI inflammation
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what do patients w/ ankylosing spondy usually present with?
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low back symptoms
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describe low back symptoms of ankylo spondy (7)
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stiffness, dull pain, persistent, worse in AM/inactivity, better w/ activity, awakens px in night, insiduous
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what are syndesmophytes?
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ossification of the outer portion of the vertebral disk
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pathogenesis of ankylosing spondy
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squared off vertebrae (erosion of corners), syndesmophytes, bamboo spine, ankylosis
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where does peripheral arthritis in akylosing spondy occur?
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hips/shoulders, small bones of hands/feet, enthesopathy
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Diagnosis of ankylosing spondy
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inflammatory low back pain and radiographic evidence of bilateral sacroiliitis
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2 spinal complications of ankylosing spondy
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fractures, C1-C2 subluxation
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General treatment principles of ankylosing spondy
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NSAIDs, Anti-TNF, avoid systemic steroids, quick tx of anterior uveitis, physical therapy
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infections known to trigger Reactive Arthritis (5)
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C. trachomatis, shigella, salmonella, yersinia, campylobacter
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how long after infxn does reactive arthritis appear?
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1-4 weeks
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are cultures of joint synovium sterile?
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YES, but leftover antigenic material may still be present
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clinical features of Reactive Arthritis
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asymmetric oligoarth, lower extremities, enthesopathy
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extrarticular manifestations of Reactive Arthritis
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urethritis, cervicitis, conjuntivitis, uveitis, oral ulcers, keratoderma blenorrhagica, circinate balanitis, nail changes
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what is keratoderma blenorrhagic?
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hyperkeratotic, psoriatic like skin lesion, usu on soles of feet
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general principles of management of reactive arthritis
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NSAIDs, abx don’t help
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