Transcript Infectious_Arthritis

INFECTIOUS
ARTHRITIS:
Overview - Part I
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Synovial Fluid Analysis
Bacterial (Nongonococcal Arthritis)
Disseminated Gonococcal Infection (DGI)
Acute Rheumatic Fever
Prosthetic Joint Infections
Overview - Part II
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Viruses that cause arthritic symptoms
Mycobacterial Arthritis
Fungal Arthritis
Parasites
Spirochete (Lyme/Syphillis) Arthritis
Synovial Fluid Analysis
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Normal Joint Fluid
highly viscous
 clear
 essentially acellular (WBC < 200)
 protein concentration approximately one-third of
plasma
 glucose concentration similar to that of plasma
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Synovial Fluid Analysis
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Non-inflammatory Joint Fluid (Type I)
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osteoarthritis, trauma, osteochondritis dissecans, neuropathic
arthropathy, subsiding or early inflammation, hypertophic
osteoarthropathy, pigmented villonodular synovitis
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also, scleroderma, SLE, and rheumatic fever which can cause
inflammatory effusions as well
highly viscous
200-2000 WBCs/mm3
yellow
Synovial Fluid Analysis
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Inflammatory Joint Fluid (Type II)
rheumatoid arthritis, crystal-induced synovitis,
seronegative spondyloarthropathies, rheumatic fever,
SLE, hypertrophic osteoarthropathy, and
scleroderma
 low viscosity
 yellow to opalescent
 2000 to 10K WBCs/mm3 (> 50% PMNs)
 increased total protein, decreased glucose
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Synovial Fluid Analysis
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Septic Joint Fluid (Type III)
bacteria, mycobacteria, or fungus
 variable viscosity, yellow to green
 50 - 150K WBCs/mm3 (> 75% PMNs)
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lower cell counts in some immunocompromised
patients, mycobacteria infections, some Neisserial
and several gram + organisms
increased total protein, decreased glucose, however
of limited diagnostic value
Synovial Fluid Analysis
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Hemorrhagic Joint Fluid
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hemorrhagic diathesis, trauma with or without
fracture, neuropathic arthropathy, PVNS, benign
neoplasms
Bacterial (Nongonococcal)
Arthritis
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Most dangerous/destructive form of acute arthritis
Predisposing Factors
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Most cases result from hematogenous spread
IV drug use, indwelling catheters, and an underlying
immunocompromised state (i.e., HIV, organ transplant pts,
diabetes, neonates, and elderly)
May be the presenting sign of infective endocarditis
(consider in IV drug abusers, or septic arthritis due to Staph
aureus, enterococci, or streptococci without obvious
predisposing cause)
Bacterial (Nongonococcal)
Arthritis
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HIV: does not occur more often, however, in advanced HIV,
more atypical infections like mycobacteria and fungal disease
in addition to staph aureus.
Underlying arthritis: bacteremia is more likely to localize in
a joint with preexisting arthritis, particularly if associated with
synovitis
 Especially rheumatoid arthritis, but also increased risk
with gout, pseudogout, osteoarthritis, and Charcot’s
arthropathy
 RA: prior intra-articular steroid injections and
maintenance immunosuppressive medications
Bacterial (Nongonococcal)
Arthritis
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Other
 direct trauma or inoculation/skin infection
 prosthetic joints
 recent joint surgery
 sternoclavicular arthritis as a rare complication of
subclavian vein catheterization
 hip arthritis from venipuncture or ruptured colonic
diverticular disease
 hemoglobinopathy
Bacterial (Nongonococcal)
Arthritis
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Pathogenesis
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Bacteria deposit in synovial membrane >>> acute
inflammatory response which spills over to synovial fluid
>>> marked hyperplasia of the lining cells within 2-7 days
with release of cytokines and proteases >>> cartilage
degradation and cartilage synthesis inhibition >>>
sometimes pressure necrosis from large effusion resulting in
further cartilage and bone loss
Bacterial (Nongonococcal)
Arthritis
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Microbiology
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Most monomicrobial infections (staph/strep > gram
negatives)
polymicrobial rare (penetrating trauma, acute diverticulitis)
Staph aureus: most common in adults (80% of joint
infections in RA)
Gram negative bacilli: IV drug abusers, neonates, elderly,
major immune deficiency (also get staph)
IV drug abusers have a predilection to develop bacterial
arthritis in axial joints
H. influenza, once common, now rare (vaccine)
Strep pneumo small % but significant
Bacterial (Nongonococcal)
Arthritis
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Clinical Manifestations
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Mono-articular arthritis (differentiate clinically from bursitis)
knee > 50% of cases, also wrists, ankles, hips
20% oligo (2-4): more common in RA, other systemic
connective tissue disease, and overwhelming sepsis
most pts febrile, although chills and spiking fevers unusual
and elderly pts may be afebrile
sometimes evidence of associated skin, urinary tract, or
respiratory infection
Bacterial (Nongonococcal)
Arthritis
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Diagnosis
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Identification of bacteria in the synovial fluid (gram stain,
culture) and leukocyte count/differential
Closed needle aspiration vs. CT/Ultrasound/ Fluoroscopic
guidance vs. sometimes surgical arthrotomy (hip/sacroiliac
joints)
Synovial Fluid: positive culture in majority of cases (can be
negative if recent antibiotics or fastiduous organism such as
some streptococci or mycoplasma)
 Gram stain: positive in most cases (75% staph aureus,
50% gram negatives, 25 % gonnococcal)
Bacterial (Nongonococcal)
Arthritis
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Diagnosis
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Blood cultures: positive in 50% of cases, should get in every
pt suspected of having bacterial arthritis
Other labs: increased WBC count and elevated ESR
(common, not specific)
Radiographs: usually normal at presentation, but should be
obtained to rule out rare associated osteomyelitis or
concurrent joint disease and for baseline
Bacterial (Nongonococcal)
Arthritis - Diagnosis
Bacterial (Nongonococcal)
Arthritis - Therapy
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Appropriate antimicrobials and adequate joint
drainage
Antibiotic Therapy
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Gram stain with gram positive cocci:
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vancomyicn (30 mg/kg IV bid)
Switch to beta-lactam therapy if susceptible
Gram stain negative
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Immunocompetent: vancomycin
Immunocompromised or traumatic: vancomycin plus 3rd
generation cephalosporin
Bacterial (Nongonococcal)
Arthritis - Therapy
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Gram stain with gram negative bacilli: 3rd generation
cephalosporin
 Add aminoglycoside if pseudomonas aeruginosa
suspected (IV drug abusers)
Modify based on culture results
Duration
 Generally 14 days parenteral, then 14 days oral
 If susceptible to fluoroquinolone, may shorten IV to 4-7
days followed by 14-21 days oral
 3-4 weeks for pseudomonas or enterbacter species
 Consider 4 week course of parenteral if documented
bacteremia (staph)
Bacterial (Nongonococcal)
Arthritis - Therapy
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Joint Drainage: Arthroscopy vs. Closed needle
aspiration
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Arthroscopy often preferred in knee or shoulder infections
because of easier irrigation and better visualization of the
joint
Initial open surgical drainage is usually necessary in hip
Serial synovial fluid analysis should demonstrate that the
fluid has become sterile and total leukocyte count is
decreasing
Rapid mobilization to prevent contractures and optimal
nutrition to the articular cartilage
Bacterial (Nongonococcal)
Arthritis
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Adverse Prognostic Factors
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Prior joint damage
Virulence of the infecting organism
Older age
Infected joint containing synthetic material
DELAYED TREATMENT!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!
Mortality Related To
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Advanced age
Coexistent renal or cardiac disease
Immunosuppression
Disseminated Gonococcal
Infection (DGI)
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Occurs in 1-3% of patients infected with Neisseria
Gonorrhoeae
Most are less than 40 years of age
Majority of pts have arthritis or arthralgia
Common cause of acute nontraumatic monoarthritis or oligoarthritis in young, healthy pts
Unique clinical features vs. other infectious arthritis
Disseminated Gonococcal
Infection (DGI)
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Pathophysiology and Predisposing Factors
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Host Factors
 female > male 3:1
 Men who have sex with men
 asymptomatic mucosal infection
 recent menstruation
 pregnancy or the immediate post-partum state
 congenital or acquired complement deficiencies (C5,
C6, C7, or C8)
 systemic lupus erythematosis
Disseminated Gonococcal
Infection (DGI)
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Microbial Factors (associated strains)
 low molecular weight protein 1A (serotype 1A)
 require arginine, hypoxanthine, uracil for growth
 usually highly sensitive to penicillin, however some
penicillinase producing
 fail to express outer membrane Protein II (transparent)
Immune Factors
 Frequent absence of positive blood, skin, and synovial
fluid cultures/subgroup with negative PCR
 gonococcal cell-wall components, antibody, complement,
and immune complexes in skin lesions
Disseminated Gonococcal
Infection (DGI)
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Clinical Manifestations (usually one of two classic
syndromes)
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1. A triad of tenosynovitis, dermatitis, and polyarthralgias
without purulent arthritis
 fevers, chills, generalized malaise
 tenosynovitis: wrists, fingers, ankles, and toes
 skin
 usually pustular or vesiculopustular
 can have hemorrhagic macules, papule, nodules
 transient, commonly only 2-10 in number, and even
without treatment, only last 3-4 days
Disseminated Gonococcal
Infection (DGI)
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2. Purulent arthritis without associated skin lesions
 most patients afebrile
 knees, wrists, and ankles most common
 polyarthritis, when present, usually asymmetric
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separation is not always absolute
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1 may evolve to 2
rare manifestations
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endocarditis, meningitis, osteomyelitis
Disseminated Gonococcal
Infection (DGI)
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Laboratory Studies
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mean synovial fluid count: 50K WBCs/mm3, however <
10K may be observed
synovial fluid cultures (positive less than 50%)
urethral/cervical, rectal cultures, increase yield to 80%
draw at least 2 sets of blood cultures if DGI suspected
 positive in less than 1/3 of DGI patients, usually in those
with the triad form
 look for staph aureus and Neisseria meningitidis
skin or tenosynovial fluid cultures usually sterile
check HIV, hepatitis, and syphilis serologies
Disseminated Gonococcal
Infection (DGI)
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Initial Treatment (parenteral)
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Oral if refuses hospitalization or mild dz but give one dose
parenteral at least
ceftriaxone 1 g IV or IM q 24 hours
cefotaxime 1 g IV every 8 hours
spectinomycin 2 gm IM every 12 hours (PCN allergic)
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Not available in the U.S.
Quinilones (resistance, CDC no longer recommends)
Duration (no controlled clinical trials)
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minimum of 3 days or until clinical symptoms are gone
“triad patients” usually cured after 3 days of therapy
Disseminated Gonococcal
Infection (DGI)
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Joint Drainage
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for “purulent arthritis”
repeated needle aspirations or arthroscopically if continued
effusions, leukocytosis, fever, severe pain
Step-Down to oral treatment
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“purulent arthritis” up to 7-14 days
CDC Guidelines: minimum treatment course of 7 days with
a switch to oral 24 -48 hours after improvement
cefixime (400 bid), cipro (500 bid)
amoxicillin (500 qid) or doxycycline (100 bid) if sens.
Treat partners if needed
also the possibility of concurrent chlamydia
Acute Rheumatic Fever (ARF)
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“migratory arthritis is generally considered the classic
feature of rheumatic fever. While it is common,
especially in the young adult patient, no one symptom
offers greater diagnostic difficulty, whether the joint
changes are objective or mere subjective complaints”
Jones
Acute Rheumatic Fever (ARF)
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Delayed non-supporative sequela of a pharyngeal
infection with Group A streptococcus
Pharyngitis usually occurs two to four weeks before the
onset of ARF symptoms
Clinical illness is self-limited, but damage to heart
valves may be chronic and progressive
Acute Rheumatic Fever (ARF)
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Pathogenesis
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Acute attack precipitated by infection of pharyngeal tissue by
group A streptococci in genetically predisposed individuals
Certain HLA-DR antigens (DRB1*16 allele)
Organ inflammation is mediated by an aberrant immune
response to certain streptococcal cellular antigens
>> formation of cross-reacting antibodies or a cell-mediated
immune response that recognizes and reacts with related
antigens present in the tissue of affected organs
Acute Rheumatic Fever (ARF)
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Clinical Manifestations
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occurs most frequently in children 4-9 years of age
onset is acute febrile illness manifested in one of several ways
(major criteria) or combination:
migratory arthritis (large joint predominant)
carditis and valvulitis
central nervous system involvement (Sydenham chorea)
rash
subcutaneous nodules
Acute Rheumatic Fever (ARF)
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Arthritis
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classically affect several joints in quick succession, each for a
short time = MIGRATORY
knees, ankles, elbows, and wrists most common
leg joints typically first; sterile inflammatory joint fluid
more common/severe in teenagers/young adults
usually the earliest symptomatic manifestation
joint pain often more prominent than objective signs
(“pseudoparalysis”)and almost always transient
6-16 joints (each joint usually no longer than 1 week)
usually very responsive to salicylates or nsaids
Acute Rheumatic Fever (ARF)
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Carditis
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pancarditis (peri, epi, myo, and endocardium)
mitral regurgitation is most common murmur
isolated aortic regurgitation and hemodynamically significant
stenotic lesions of the aortic/mitral valves unusual at
presentation (mitral stenosis = sequele)
severe valvular damage and myocardial dysfunction from
myocarditis can lead to CHF
Lab:
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EKG: all degrees of heart block
Cardiomegaly on CXR
Echocardiography: nearly all pts have signs of acute carditis
Acute Rheumatic Fever (ARF)
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Sydenham’s Chorea
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abrupt, purposeless, nonrhythmic involuntary movements,
asymmetrical, sometimes unilateral
muscular weakness
emotional disturbances
no sensory loss or involvement of the pyramidal tract
diffuse hypotonia may be present
may have a longer latent period vs. other rheumatic
manifestations, up to 8 months
some patients may have no other symptoms
Acute Rheumatic Fever (ARF)
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Subcutaneous Nodules
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firm and painless
overlying skin noninflamed and movable
few millimeters to two centimeters in diameter
over bony surface or near tendons
single lesion to a few dozen, mean 3-4, symmetric
one or more weeks, rarely greater than one month
smaller and more short-lived than RA nodules
usually only in patients with carditis
Acute Rheumatic Fever (ARF)
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Erythema Marginatum
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evanescent, non-pruritic rash, pink or faintly red
trunk, sometimes proximal limbs, not face
lesions extend centrifugally while skin in center returns to
normal
early in disease
persists or recurs when all other manifestations have
disappeared
occurs only in patients with carditis
Acute Rheumatic Fever (ARF)
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Modified Jones Criteria, 1992
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Major manifestations: carditis, polyarthritis, Sydenham
chorea, erythema marginatum, subcutaneous nodules
Minor manifesations:
Clinical: fever, arthralgia
 Laboratory: elevated acute phase reactants (ESR,CRP), prolonged
PR interval
Supporting evidence of antecedent Group A streptococcal infection
 Elevated or rising streptococcal antibody titers (ASO, DNAase,
hyaluronidase, streptokinase)
 Positive throat culture or rapid streptococccal antigen test
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High probability of ARF if 2 Major, or one major and
two minor with evidence of Group A streptococcal
infection
Acute Rheumatic Fever (ARF)
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Modified Jones Criteria, 1992
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3 settings where diagnosis can be made without strict
adherence to criteria
Chorea as the only manifestation
 Indolent carditis as the only manifestationi in patients
who come to medical attention months after the acute
infection
 Recurrent rheumatic fever in patients with h/o rheumatic
fever or rheumatic heart disease
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Acute Rheumatic Fever (ARF)
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2002 AHA Update
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Concluded that there were insufficient data to support a
revision of 1992 criteria
If pre-existing rheuamtic heart disease, use caution in
interpreting a single clinical finding as a sign of recurrence of
rheumtic fever
Strict adherence in areas of high prevalence may result in
underdiagnosis
Agreed that echocardiography in diagnosis of acute rheuamtic
fever was controversial in patients without cardiac findings
on physical exam
Acute Rheumatic Fever (ARF)
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Treatment
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Symptomatic Relief
Eradication of Group A beta-hemolytic streptococcus
Prophylaxis against future infection to prevent recurrent
cardiac disease
Acute Rheumatic Fever (ARF)
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Symptomatic Relief
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Anti-inflammatory agents, most commonly aspirin, usually provide
dramatic improvement of arthritis and fever (80-100 mg in children, 4 – 8
g/day in adults, serum conc. 20-30 mg/dl)
Rash usually temporary and does not need treatment
Carditis (severe disease = significant cardiomegaly, CHF, or third-degree
heart block)
 Conventional therapy for heart failure
 Steroids 2 mg/kg/day 1-2 weeks, then taper over 1-2 weeks, however
studies of benefit conflicting
Acute Rheumatic Fever (ARF)
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Antibiotic Therapy
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Penicillin oral for 10 days or one time IM at time of diagnosis
regardless of presence or absence of phayrngitis
PCN allergic: oral erthryomycin or cephalosporin
Throats of all family contacts should be cultured and treat
with PCN if positive for B-hemolytic strep
Acute Rheumatic Fever (ARF)
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Antibiotic Prophylaxis
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Goal: to prevent recurrence of ARF
Oral: PCN VK 250 mg twice per day; alternative sulfadiazine 500-1000
mg per day, or e-mycin 250 mg bid
Parenteral: benzathine PCN G 0.6-1.2 million units IM every 4 weeks
(every 3 weeks may be more effective)
Duration: unclear
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Until pt is a young adult (18-20 years), usually 10 years from acute attack with
no recurrence
Indefinite if documented evidence of rheumatic heart disease or continued
exposure to B-hemolytic group A strep population
Prosthetic Joint Infections
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Epidemiology
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Rate 0.5-1.0% for hip replacements and 0.5-2% knee
Re-infection remains major problem in patients undergoing replacement
arthroplasty
Risk Factors (early infection)
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RA or other systemic illness, perioperative or nonarticular infections,
prior infection of the joint or adjacent bone, prior surgery on joint,
prolonged duration of surgery, higher number of O.R. personnel,
postoperative bleeding or hematoma formation, advanced age
Prosthetic Joint Infections
Pathogenesis
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Early-Onset Infections
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Late-Onset Infections
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Within first 2 months after surgery
Contamination of operative wound by bacteria on the skin of the
patient or airborne in the operating room
> 75% due to staph species or other gram positives
Hematogenous seeding at the surface of bioprosthetic materials and
damaged joint tissues
Postoperative wound dehiscence may develop infection of
prosthesis by contiguous spread of organisms such as gram
negative rods
Prosthetic Joint Infections
Pathogenesis
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The Role of Biofilms
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Adherent bacteria to prosthetic joint multiply and elaborate
exopolysaccharides, also known as glycocalyx
Microcolonies of bacteria encased in glycocalyx coalesce to
form a biofilm
Bacteria deep within biofilm are metabolically inactive or in
various stages of dormancy and protected from host
defenses; typically highly resistant to antimicrobial agents
(time-related)
Delay of infection, treatment failure,clinical relapses
Prosthetic Joint Infections
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Microbiology
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Early infection: majority coagulase negative staph, however
staph aureus still important
Late Infection: staph aureus most common
Clinical Manifestations
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Early infection: pain; erythema, induration, and edema at the
primary incision; wound drainage; fever common
Late infection: prolonged indolent course, primarily joint
pain, rarely fever, leukocytosis, or symptoms of infection
at another site
Prosthetic Joint Infections
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Diagnosis
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Acute-phase reactants: usually elevated, non-specific
Radiographs
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loosening of prosthesis in late-onset infections only and is
nonspecific as aseptic loosening can be due to mechanical causes
Periosteal new bone formation highly suggestive but infrequently
present
Bone scan: nonspecific in early infections, and can be positive in a
small number of patients with aseptic loosening
Prosthetic Joint Infections
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Joint Fluid Analysis
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usually diagnostic in early-onset infections
Biopsy of Joint Tissue or Periarticular Bone
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Intraoperative frozen section histology
Sometimes required to diagnose late-onset infection
Several sections should be sent routinely during elective revision
arthroplasty even if infection is not suspected
Prosthetic Joint Infections
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Treatment
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Early-onset: surgical debridement with long course of IV
antibx curative between 25 and 33%
Late-onset: vast majority need removal of prosthesis,
particularly if it is loose
Replacement Arthroplasty: one vs two stage
Arthrodesis
Suppressive Medical Therapy
A small number ultimately require amputation
Prosthetic Joint Infections
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Prevention
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Preoperative antibiotics: cephazolin or cefuroxime vs.
vancomycin
Screen for occult or minor infections
Treat wound infection or skin necrosis early
Unclear benefit: laminar flow in O.R., body-exhaust surgical
suits, antibiotic-impregnated cements
NO EVIDENCE TO SUPPORT ANTIBIOTIC
PROPHYLAXIS PRIOR TO DENTAL OR
UROLOGIC PROCEDURES
QUESTIONS?