Download Septic (Infectious) Arthritis- Intro

Septic (Infectious) Arthritis- Intro- synovial inflammatory rxn secondary to direct
invasin of joint space by bac, viruses, mycobac, and fungi
o Acute- caused by pyogenic bacteria. Termed as septic or suppurative arthritis.
 Gonococcal vs non-gonococcal
 Neisseria gonorrhea  hemogenous spread. Less morbidity
associated with this.
o Most common ages 18-35
o 4x more common in women (gonorrhea is more often
asymptomatic in womenleft untreated)
 Non-gonococcal—S. aureus is most common. Rapidly destructive.
Significant morbidity and mortality.
o Children <5 and adults >64
 Adult predisposing factors- prosthetic joint,
rheumatoid arthritis, a comorbidity such as
malignancy, diabetes mellitus, use of
immunosuppressive medications, skin infection.
o Chronic- caused by slowly progressive organisms such as mycobacteria and
fungi
o Usually large, monoarticular joints.
Non-Gonococcal Arthritis
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o Hematogenous seeding is most common—synovial membrane is highly vascular
and lacks a basement membrane
 Sources: Infections or invasive procedures of the skin, respiratory,
urinary systems, or oral cavities, IV catheters, Illicit IV drugs
o Direct Inoculation—2nd most common.
 Prosthetic joint infection from operative procedure, or direct inoculation
of native joints from surgical procedure, trauma, bite, or FB puncture into
joint space.
o Contiguous Source—osteomyelitis (most common in children)
o Infants less than 1 year—metaphyseal blood vessels that traverse the
growth plate can act as a conduit for infection.
o Older children—can break the outer cortex secondary septic
arthritis
o Adults—skin infection and DM foot ulcers are most common
o Staphlococcus epidermis—coagulase negative. Major isolate in early-onset
prosthetic joint infection.
o Streptococcus spp. —2nd most common in adults and children. Group B Strep >
Group A step and S. pneumoniae
o Gram Neg. Bacilli—Pseudomonas aeruginosa and E. Coli. IV drug users, young
children, elderly, immunocompromised, and those with extra-articular
infections.
Pathenogenesis of Septic Arthritis
o Multifactorial
o Synovium is highly vascular without basement membrane easy hematogenous
spread
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o Joint space is largely avascular due to hyaline cartilage, and low fluid shear
conditions, which are favorable for bacterial growth.
o Colonization factors:
 Tissue tropism of the bacteria
 Bacterial receptors that mediate adherence (S. aureus):
fibrinogen-binding proteins, fibronectin-binding proteins,
collagen receptor, elastin-binding protein, bone sialoprotein
adhesion, and protein A.
o Virulence:
 Capsular polysaccharides- interfere with opsonization and phagocytosis
 Microcapsule- important in early colonization of the joint by allowing
staphylococcal adhesion factors to bind to host proteins
 Staphylococcal wall peptidoglycans (N-formyl-methionine proteins and
teichoic acids)- potent mediators of joint inflammation through binding of
TLRs.
o Host Immune Response:
 Il-1beta and IL-6 contribute to inflammatory response Acute-phase
proteins released from liver to activate complement system
 TNF-alpha neutrophil recruitment, followed by
macrophages/monocytes
 If infection is not rapidly cleared, then immune response elevated
inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and granulocyte
macrophage colony stimulating factor), and with ROS in joint space 
rapid joint destruction.
 Neutrophils release metalloproteinases and lysosomal and proteolytic
enzymes  degeneration of articular cartilage, then destruction of
subchondral bone (can happen in as little as 3 days.)
 N. gonorrhea elicits a mild influx of neutrophils and therefore results in
minimal joint destruction
 Synovial effusion can develop in bacterial arthritis increased pressure
and less ability to get blood and nutrients to the joint further
destruction of joint
Risk Factors
o Non-gonococcal: Age, underlying joint disease, prosthetic joint, DM, skin
infections
 Old age- weaker immune responses, more chronic diseases
 Joint disease- RA and prosthetic joints ^ likelihood for bacteria to
invade
 DM- reduces body’s ability to defend pathogens
 Skin infection- increased risk of bacteremia
Clinical Manifestations
o Fever, malaise, single joint that is hot, red, severely painful, swollen, marked
decreased ROM due to obvious synovial effusion.
 Monoarticular—Knee is most common>hip>shoulder> ankle=wrist
 Oligoarticular = 10% of non-gonococcal
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Lab Findings
o + blood cultures 50% of the time
o Leukocytosis with a left shift
o ESR and CRP ^
Synovial fluid findings
o Opaque
o WBC >50,000 with neutrophil prominence of 75-80%
o Glucose concentration is usually at least 50% below blood glucose level
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Imaging Studies
o Plain xray usually normal—soft tissue swelling with widening of joint space
 Later films—joint space narrowing as cartilage is destroyed. Loss of
visualization of the white cortical line over joint surface
o Ultrasound—sensitive for detection of joint effusion; not reliable to
determine cause
o CT and MRI—to distinguish osteomyelitis, peri-articular abscesses, and joint
effusions. MRI preferred. Can determine jnt effusion, jnt space narrowing,
bone and cartilage erosions, gas within the joint, and soft tissue swelling.
Treatment
o Antimicrobials, drainage, immobilization for pain control
o Antibiotics
 Based on likelihood of the organism involved, then later modified, if
needed, after results of culture and gram staining come in
o Drainage
 Needle aspiration initially up to 2-3x a day if necessary to prevent
accumulation
 Percutaneous drainage
 Surgical- when percutaneous drainage and antibiotics fair to clear
infection in 5-7 days
o Joint Mobilization
 Isotonic exercise—prevents muscle atrophy and facilitates healing
Gonococcal Arthritis
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o Complication of the STD, gonorrhea (gram negative diplococci, Neisseria
gonorrhea)
 Women- endocervix and urethra; Men- epididymis
o Dissemination from mucosal primary site—joint is most common site of
dissemination, but only 1-2% of gonorrhea disseminates hematogenously
Risk Factors
o N. Gonorrhoeae virulence, diagnosis delay, complement system deficiency,
SLE, female, menstruation, pregnancy, male homosexuality, and low SES and
educational status.
o Virulence
 Antigenic variation of gonococcal pili
 Protein IA and IB—A= disseminated infections; localized infections
 Protein II—avoids immune clearance
 Protein III
 Lipo-oligosaccharide—synovial damage
o Complement deficiency—13% of disseminated gonorrheal infections (DGI)
o Females—4x as likely to develop DGI as males, and menstruation is a risk
factor as well
Clinical Manifetsations
o Time from initial infections to initial manifestations of arthritis range from 1
day to 2 months (surprise!)
o Prodromal signs—Migratory arthralgias which are polyarticular,
asymmetric, tend to involve upper extremities, and tend to resolve
spontaneously in 30-40% of cases or evolve into septic arthritis
o Tenosynovitis—rare in other forms of septic arthritis*, so it is a clue to DGI.
 Inflammation of synovial sheath
 Pain, swelling, difficulty moving joint
 Asymmetric
 “lover’s heels” when it involves the Achilles tendon… (umm.. ok?)
o Dermatitis—
 Extremities and trunk; not the face
 Maculopapular, pustular, or vasicular lesions less than 5mm on
erythematous base
 Center may become necrotic or hemorrhagic.
 Painless and
nonpruritic
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o Purulent Arthritis—within days to weeks of gonoccoccal infection
 More than one joint—knees, wrist, elbows
 Inflammatory signs
 Mean WBC is 50,000 and is lower compared to non-gonococcal
arthritides*
o Non-specific constitutional symptoms: Fever, myalgias, malaise
Lab Studies
o Gram stain—gram neg. intracellular diplococci
o Culture of N. gonorrhoeae
o Synovial fluid gram stain is + in 25% of cases; and their cultures are positive
in 50% of cases (picky growth requirements)—chocolate agar and CO2 rich
environment.
 Thayer-Martin Agar- 3 antibiotics to kill off everything but N.
gonorrhea.
Pathogenesis
o Clinical presentation of DGI resembles serum sickness with tenosynovitis
and migratory arthralgias—often transient and disappear without treatment
o Other differentials: viral hepatitis
o Suggested role of immune-mediated hypersensitivity in synovitis and
dermatitis associated with DGI—presence of circulating immune complexes
o Deposition of circulation gonococcal antigen-antibody complexes due to
DGI seeding in the joint and therefore gonococcal arthritis
Tuberculous Arthritis
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^ HIV and anti-tuberculous drug resistance increased prevalence of this arthritis
o 2/3 of HIV pts have TB
Anti-TNF drugs for RA have also lead to ^ in TB
Pathogenesis
o Direct invasion from adjacent TB osteomyelitis
o Hematogenous dissemination from primary focus (lungs, lymph, or viscera)
Risk Factors
o SES—elderly with compromised immune systems. Also living
situations/environmental exposures and ethnic minorities and immigrants
from countries with high incidence of TB
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o Immunocompromised—HIV, DM, malnutrition, alcohol, debilitating illness,
corticosteroid therapy, immunosuppressive and cytotoxic drugs
o Local joint and bone tissue factors—joint/bone trauma can lead to
reactivation of the disease. Ex IV drugs, surgery, RA, SLE, Sjogren syndrome,
gouty arthritis, prosthetic joint, osteonecrosis
Clinical Presentation
o Chronic monoarthritis in large and medium weight-bearing joints
 Hip and knee most common; men 50+
o Chronic progressive low-grade joint pain and swelling without warmth or
erythema and stiffness with slowly progressive loss of fn, often with eventual
abscess formation. Fever, night sweats, weight loss and anorexia may be
present.
Imaging
o Phemister Triad: periarticular osteoporosis, peripherally located osseous
erosion, gradual diminution of joint space
 In contrast: RA and pyogenic arthritis has joint space narrowing early
on
Diagnosis
o Synovial fluid—variable and do not distinguish TB from other arthridites
 Cell counts often inflammatory rather than septic in nature—may
have predominance of neutrophils
 Glucose tends to be low and more than 10mg/dL below serum levels
o Acid Fast Smear of synovial fluid—only + in 10-20% of cases
o Synovial fluid culture- 80% of cases show up +
o Open biopsy technique typical caseous granulomas
If left untreated complete joint obliteration with fibrous ankylosis of joint
Lyme Arthritis
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Borrelia burgdorferi- spirochete. Transmitted by deer tick (Ixodes).
o Early localization of infections—erythema migrans (bulls eye) within 1
month of tick bite (axilla, groin, popliteal areas)
 Expands at rate of 2-3cm per day; central clearing in larger lesions
 Lesions greater than 5cm in diameter are sufficient for est. diagnosis
of Lyme disease
 Flu-like symptoms: fever, malaise, neck pain or stiffness, arthralgias,
myalgias
o Early disseminated infection
 Within weeks of onset of infection
 Can disseminate through skin, blood, and lymph to infect multiple
tissues
 Clinically apparent disease seen in skin, heart, and nervous
system
 Debilitating fatigue and appear ill
 Skin—bull’s eye is a sign of disseminated infection. Secondary lesions
are smaller and can occur anywhere, but most noticeable on the trunk
(flat macules and can develop partial clearing)
 Can be accompanied by migratory muscle, joint, and
periarticular pain that lasts hours to days
 Cardiac—varying degrees of atrioventricular block, occasionally
accompanied by mild myopericarditis
 Nervous System—occurs in less than 10%. Meningitis: headache,
photophobia, and/or stiff neck
o Late disease
 Months after onset of infection
 Untreated pt late manifestations such as lyme arthritis and
encephalomyelitis
 Lyme Arthritis
 Clinical Presentation—months or years after B. burgdorferi
infection.
o Usually monoarthicular or oligoarticular in one or a few
large joints (fewer than 5 total). Knee most common
(big surprise).
o Joints are warm with large effusions (more than 100mL
in the knee), but with little pain.
o Recurrent episodes- smaller effusions, pannus, bony
erosion, and cartilage destruction
 Synovial fluid findings—
o Inflammatory with WBC about 24,000 with
predominance of neutrophils
 Synovial biopsy findings—depends on chronicity.
o May have only mononuclear cell infiltration
o More advanced changes—pannus, consistent with
rheumatoid synovium
o Silver stains may reveal small numbers of organisms in
vicinity of blood vessels in approx. 25% of synovial
biopsies
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Antibiotic refractory Lyme Arthritis—10% treated with
antibiotics have persistent joint inflammation and proliferative
synovitis
o May be due to induced autoimmunity.
 “It is hypothesized that specific HLA-DR
molecules bind an epitope of B. burgdorferi
outer surface protein A, which initiates a T-cell
reaction to this epitope. The T-cells may crossreact with an unknown self-antigen (an example
of “molecular mimicry”). The joints in these
patients have synovial pannus, which causes
articular cartilage destruction and permanent
deformities.”
Laboratory Findings
o Routine labs are non-specific
 Mild elevated neutrophil, ESR, and liver fn tests
Diagnosis
o Antibodies to B. burgdorferi—indicates previous exposure, but is not
necessarily evidence of active infection
 About 5% of normal human serum samples yield + results on
serologic tests for lyme disease in nonendemic areas
o Two-Tiered approach: ELISA or indirect IF to detect IgM and IgG reactivity to
the organism (initial screening test), followed by immunoblot (Western) to
confirm + or equivocal results from Ab test
Imaging
o Limited role
o Xray shows arthritic joints with changes consistent with inflammatory
arthropathy, including joint effusions, synovial hypertrophy, periarticular
osteoporosis, cartilage loss, and bony erosions
Viral Arthritis
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Inflammation of joints caused by viral infection
Etiology
 parvovirus B19; hepatitis A; hepatitis B; hepatitis C; rubella virus;
alphaviruses (togaviridae family); human immunodeficiency virus; human Tlymphotropic virus 1; Epstein-Barr virus; mumps virus; varicella-zoster virus;
adenovirus; coxsackievirus, and herpes simplex virus.
Clinical Presentation
o Symmetrical small-joint involvement
 Different viral infections can have variations
 In most cases, peripheral small joints, hands, wrists, knees, and ankle
joints, with prominent morning stiffness and fusiform swelling, but
not erythrema
o Arthritis lasts from weeks to a few months, can be severe at onset but usually
is self-limiting and progressively resolves over time
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o In all instances, viral arthritis is nondestructive and does not lead to chronic
disease
Diagnosis
o Use symptomology and serology
o Take into consideration non-rheumatic symptoms (fever, skin
manifestations, etc), medical hx, recent travel and exclusion of other
rheumatic or febrile illnesses
o PCR of synovial material can be used to ID causative agent—not always
conclusive.
o Culture is rarely used.
o Most do not result in joint changes and only show soft-tissue swelling**
Pathogenesis
o There has been speculation that autoimmune responses are induced by
infection—no convincing human data
o Mechanisms are poorly understood—appear to arise from immune
responses directed against viral antigens and pathological inflammatory
responses generated by viruses and/or their infection products residing
within joint tissues
Treatment
o NSAIDs (for pain relief), with steroids or interferon occasionally used.
Antivirals if available.
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