Flashcards in Infectious Arthritis Deck (54):
lining tissue of the synovium and all intracapsular structures, typically 1-3 cells deep
two types of synovial lining cells
intimal macrophages with increased cytoplasmic organelles and intimal fibroblasts that have decreased organelles and increased ER
what is the synovial intima lacking?
a lmiting basement membrane
what supports the synovial lining?
fenestrated microvessels in the interstitium of the subintima
contains collagen fibrils, proteoglycans, and VASCULAR SUPPLY (fenestrated blood vessels)
importance of fenestrations in subintima vascular supply
blood plasma can freely flow out into synovial lining
what is the most rapidly destructive form of joint and bone disease?
bacterial arthritis (a rheumatologic emergency!)
what are most cases of septic arthritis due to?
hematogenous spread (bacteremia) followed by direct innoculation
why is the joint susceptible to infection from hematogenous spread?
abundant vascular supply and lack of limiting membrane
ligamentous insertion into bone
two divisions of septic arthritis
gonococcal and nongonoccal
what is the most common nongonococcal bacteria causing septic arthritis?
staph aureus (gram positive clustering cocci)
risk factors for septic arthritis
age (>80), infection with bacteremia, joint disease/pre-existing damage (OA, RA), immunosuppressed state (diabetes, steroids), trauma, prosthetic joint, IV drugs, endocarditis
pathogenesis of septic arthritis
virulence factors of different bacteria sustain the infection and cause joint damage
virulence factors for s. aureus
MSCRAMMs and agr
bind host matrix proteins to enable s aureus to anchor itself in the interstitium
accessory gene regulator. regulates s aureus surface proteins and exotoxins
timeline of virulence factors in S. aureus septic arthritis
at low cell concentrations, agr up regulates cell surface proteins important for attachment. once cell growth enters stationary phase, age down regulates adhesion proteins and up regulates tissue destroying enzymes
virulence factors for N gonorrhea
pili enable attachment, outer membrane protein I inactivates complement and prevents neutrophil phagolysosomal fusion
3 ways septic arthritis leads to damage
direct effects from invading bacteria, host's own immune response, mechanical effects from pressure of joint effusion
the organism produces destructive toxins and enzymes which mediate joint damage. (hemolysins)
host inflammatory overreaction
activated inflammatory cells produce cytokines which help recruit more cells, cytokines activate MMPs, neutrophils/marophages engulf bacteria and release cytokines, which stimulate proteases and ROSs
mechanical effects causing damage
ischemia due to excess purulent exudate accumulation causing intra-articular pressure increase and reduced blood flow
clinical presentation of septic arthritis
fevers, chills, malaise, monoarticular involvement (due to cytokines)
dolor/calor/tumor/rubor (due to inflammation)
clinical presentation of gonococcal arthritis
sexually active young adults, 1 or more joints affected, DGI
disseminated gonorrheal infection: fevers, shaking chills, vesiculopustular rash, tenosynovitis, polyarthralgias
normal joint effusion
clear, colorless, viscous. <200 leukocytes
noninflammatory joint effusion (OA)
clear, yellow, viscous, leukocytes 200-2000
inflammatory joint effusion
cloudy, yellow, decreased viscosity, leukocytes 2000-100,000
septic joint effusion
purulent, markedly decreased viscosity, usually leukocytes >50,000 with mostly neutrophils
organism causing lyme disease
borrelia burgdorferi via ixides tick
three stages of lyme disease
early localized, early disseminated, late disease
in which stage of lyme disease do you see inflammatory arthritis?
early localized lyme disease
within days, bulls eye rash (erythema migrans), viral symptoms (fevers, lymphadenopathy, malaise, arthralgias, myalgias)
early disseminated lyme disease
1-3 mos after bite, cardiac and neurological symptoms (myopericarditis, Bells palsy)
late lyme disease
>3mos, main clinical feature is inflammatory arthritis (2/3 of patients who reach this stage)
which joint is typically affected in lyme arthritis
lyme arthritis pathophysiology
host inflammatory response, since borrelia doesn't produce any proteases!
what is the typical synovial leukocyte count for septic arthritis from lyme?
antibiotic resistant lyme arthritis
rare, can't detect borrelia in fluid PCR, most likely due to molecular mimicry
immune response driven by foreign stimuli that cross reacts with self elements.
support for molecular mimicry in lyme arthritis
specific class 2 MHCs are predisposed, human LFA-1a has sequence homology to borrelia OspA and activates OspA reactive T cells, patients have high titers of Abs to OspA. becomes autoimmune
problems with molecular mimicry hypothesis
LFA-1a is only a weak agonist to OspA, OspA T cells diminish in synovial fluid after antibiotic Rx in both regular and resistant lyme arthritis
clinical appearance of viral associated arthritis
acute onset, symmetric, inflammatory, polyarticular (small joints), may have rash
hep B arthritis
immune complex mediated, serum sickness
prodrome characterized by urticaria (hives), maculopapular rash, inflammatory arthritis of small joints
presumed mechanism of hep B arthriits
hep b surface antibodies form soluble immune complexes that are deposited in synovium, which activates complement and neutrophils, enzymes released by neutrophils cause damage
when does clinical disease begin in hep b arthritis?
once the circulating complexes start lowering serum complement
what is the most common viral arthritis
who is predominately affected by parvovirus b19 arthritis?
mechanism of parvovirus arthritis
parvovirus enters joint via interaction with Gb4 on synovium, antigenic persistence causes ongoing immune response