Septic Arthritis

Septic arthritis, also known as infectious arthritis, may be caused by any number of different microorganisms and results in erythematous, painful, swollen joints. Synovial (joint) fluid analysis is the cornerstone of diagnosis and should be performed before beginning antibiotic therapy. Blood or joint fluid culture may also be used to identify the microorganism causing the infection and guide subsequent treatment.

Diagnosis

Indications for Testing

  • Acute mono- or oligoarticular arthritis
  • Loosening of prosthesis

Laboratory Testing

  • CBC with differential – expect mild to moderate leukocytosis and left shift of cell composition (immature band forms)
    • Results that increase likelihood ratio (LR) for septic arthritis
      • White blood cell (WBC) count >10,000/µL = LR 1.4
      • Neutrophils >90% = LR 3.4
  • Joint aspiration (arthrocentesis) with synovial specimen (when possible) – cornerstone of diagnosis and should be performed prior to antibiotic administration
    • Aspiration should not be performed through overlying cellulitis
    • Macroscopic assessment – viscosity, color, clarity
      • Inflammatory fluid
        • Color – ranges from yellow to greenish
        • Consistency – turbid
    • WBC count with differential
      • Usually >50,000/µL with predominance of neutrophils
        • Same degree of leukocytosis may be noted in gout and pseudogout
      • WBC count >50,000/µL increases likelihood of septic arthritis (LR 7.7 positive; LR 0.42 negative)
        • At least 90% leukocytes (LR 3.4 positive; LR 0.34 negative)
        • <50,000/µL does not rule out septic arthritis
        • Low WBC count common in immunosuppressed patients
      • Prosthetic joints – cell count cutoffs are much lower   
        • Knee – WBC >1,700/µL or differential >65% neutrophils
        • Any other joint – WBC >4,200/µL or differential >80% neutrophils
    • Gram stain – low sensitivity; diagnostic if organisms are identified
    • Culture – moderately high sensitivity if positive
      • <50% positive in gonococcal arthritis – recommend diagnosis of gonococcal arthritis be made based on clinical presentation and cultures of cervix, rectum, urethra, or oropharynx
    • Crystal scan with polarized microscope – evaluate for crystalline arthritis
      • Monosodium urate demonstrates negative birefringence
      • Calcium pyrophosphate dehydrate (CPPD) crystals have weak birefringence
    • Not recommended
      • Glucose, lactate dehydrogenase (LD), and protein – neither sensitive nor specific
      • Polymerase chain reaction (PCR) for specific organisms
  • C-reactive protein (CRP)
    • Usually elevated; absence of increased concentrations does not exclude septic arthritis
    • CRP >10 mg/L (>1.0 mg/dL) increases likelihood of septic arthritis (LR 1.6)
      • CRP ≥13.5 mg/L (≥1.35 mg/dL) in prosthetic joints – sensitivity 73-91%, specificity 81-86%
      • CRP remains elevated up to 2 months postarthroplasty, then becomes normal
    • Inflammatory parameters may remain high for up to 2 weeks postsurgery
  • Cultures
    • Blood cultures
      • Positive in 50-70% of patients with nongonococcal bacterial arthritis
        • Diagnostic if positive
        • Limited usefulness but may be helpful when ruling out other diseases, particularly in children
      • Lower rate of positivity in prosthetic joints
    • Tissue cultures – prosthetic joints
      • Multiple intraoperative tissue samples should be sent for culture (ideal is 5-6)
      • Antimicrobial susceptibility testing may help guide therapy
    • Other site cultures dependent on patient history – skin ulcer, urine, throat, genitourinary
  • Other testing – serologic testing for Lyme disease in patient with negative cultures and who resides in an endemic area

Histology

Prosthetic joints – intraoperative frozen sections often show >5-10 polymorphonuclear neutrophils per high-power field (PMNs/hpf) which indicates acute inflammation.

Imaging Studies

  • X-ray/ultrasound – useful in detecting the presence of fluid; not useful in diagnosis of osteomyelitis unless late in course of disease
    • Prosthetic joints – periprosthetic lucency, osteolysis, or prosthesis migration may be seen
  • Bone scan or magnetic resonance imaging (MRI) – may be necessary to rule out osteomyelitis
    • Sensitive for detecting failed implants but not specific for infection
    • Artifact from implants may obscure information

Differential Diagnosis

  • Adult noninfectious inflammatory arthritis
  • Pediatric inflammatory arthritis
    • Kawasaki disease
    • Toxic (or transient) synovitis
    • Slipped capital femoral epiphysis
    • Acute rheumatic fever
    • Legg-Calvé-Perthes disease (LCPD)
    • Osteochondrosis
    • Sickle cell disease
  • Intra-articular injury
    • Fracture
    • Meniscal tear
    • Osteonecrosis
    • Traumatic effusion
    • Hemarthrosis
  • Other
    • Malignancy (eg, synovial sarcoma)
    • Osteomyelitis
    • Cellulitis overlying joint

Monitoring

C-reactive protein (CRP) levels – nonspecific, but often elevated during infection.

Background

Epidemiology

  • Incidence – 2-10/100,000 in the U.S.
    • 30-40/100,000 in patients with rheumatoid arthritis
    • 40-70/100,000 in patients with prosthetic joints
  • Transmission
    • Most cases are hematogenously acquired
    • Other mechanisms for infection
      • Surgery
      • Trauma
      • Percutaneous puncture
      • Spread from contiguous structure infection

Commonly Involved Organisms 

  • Bacteria
    • Children
    • Adults
      • S. aureus – most common (50% of cases)
      • Streptococcus spp (groups A and B)
      • Neisseria gonorrhoeae – almost exclusively in sexually active patients
      • Gram-negative bacilli – elderly, intravenous (IV) drug abusers, immunocompromised persons
        • E. coli
        • Pseudomonas aeruginosa
        • Salmonella – sickle cell disease, immunocompromised
      • Coagulase-negative staphylococci – prosthetic joint
      • Listeria (rare) – rheumatoid arthritis, immunosuppression
      • Anaerobes (rare) – prosthetic joints, bite victims
      • Polymicrobial – up to 20% of arthroplasty patients; most commonly methicillin-resistant S. aureus (MRSA) or anaerobes plus other organisms
      • Borrelia burgdorferi – areas where tick is endemic
  • Virus – rare; most common is parvovirus B19
  • Fungi – uncommon
    • Endemic dimorphic fungi
    • Candida spp – immunocompromised persons
  • Parasites – rare
    • Helminths
    • Filaria

Risk Factors

  • Nonprosthetic joint
  • Prosthetic joint
    • Patient related
      • Previous arthroplasty
      • Tobacco abuse
      • Obesity
      • Rheumatoid arthritis
      • Diabetes mellitus
      • Immunosuppression
      • Bacteremia, endocarditis
    • Surgery related
      • Simultaneous bilateral arthroplasty
      • Operative time >2.5 hours
      • Allogenic blood transfusion
      • Postoperative complications
        • Delayed wound healing
        • Atrial fibrillation
        • Myocardial infarction
        • Urinary tract infection (UTI)
        • Prolonged hospital stay

Pathophysiology

  • Organism accesses joint space either directly or hematogenously
  • Organisms cause release of inflammatory cell cytokines, proteases
    • Leads to destruction of cartilage, inhibition of new cartilage synthesis, and bone loss

Clinical Presentation

  • Fever
  • Warm, swollen, erythematous, painful joint
  • Prosthetic joint
    • Draining sinus
    • Loosening of prosthesis
    • Pain in the area around the prosthesis
  • Infection may disseminate systemically

ARUP Laboratory Tests

Initial screening test in septic arthritis

May assist in evaluating for joint disease, systemic disease, or inflammation

Detect white blood cells (WBCs) and presence and type of microorganisms in specimen

Important informationLimited to the University of Utah Health Sciences Center only

Identify bacteria in normally sterile body fluids

May assist in differentiating gout from septic arthritis

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical culture; refer to anaerobe culture and gram stain

For CSF specimens, order CSF culture and gram stain

For blood specimens, order blood culture or blood culture, AFB and fungal

Anaerobe culture is NOT included with this order

Preferred test to detect acute phase inflammation (eg, autoimmune diseases, connective tissue disease, rheumatoid arthritis, infection, or sepsis)

Important informationLimited to the University of Utah Health Sciences Center only

Use to detect presence of bacteria in blood

Time-sensitive test

Important informationLimited to the University of Utah Health Sciences Center only

Identify bacteria in tissues

Anaerobe culture is recommended for body fluids, tissue, and deep wound/surgical cultures; refer to anaerobe culture and gram stain

Anaerobe culture is NOT included with this order

Related Tests

May be helpful in initial diagnosis of septic arthritis

Normal erythrocyte sedimentation rate (ESR) does not rule out septic arthritis

Preferred reflex test to detect Lyme disease in individuals with ≤4 weeks of clinical symptoms or exposure to tick

Consider in patient with negative cultures and who resides in an endemic area

Reflex pattern: if enzyme-linked immunosorbent assay (ELISA) result is 1.00 LIV or greater, then IgG and IgM immunoblot will be added

Intended for use in suspected periprosthetic joint infection

Medical Experts

Contributor

Fisher

Mark A. Fisher, PhD, D(ABMM)
Associate Professor of Clinical Pathology, University of Utah
Medical Director, Bacteriology, Special Microbiology, and Antimicrobial Susceptibility Testing, ARUP Laboratories

References

Additional Resources