Septic Arthritis

Epidemiology and Etiology

Epidemiology

• Incidence: 2–6 cases per 100,000 people in the United States
• More common in children than adults: peaks between the ages of 2 and 3 years
• 2:1 male predominance

Etiology

The majority of septic arthritis infections are monomicrobial. Common organisms include:

• Staphylococci:
  • Staphylococcus aureus (most common)
  • S. epidermidis
• Streptococci:
  • Streptococcus pyogenes
  • S. pneumoniae
  • S. agalactiae
• Gram-negative bacteria: 
  • Pseudomonas aeruginosa
  • Escheria coli
  • Kingella kingae
  • Neisseria gonorrhoeae
  • Haemophilus influenzae
  • Salmonella species

Risk factors

• Infants and children:
  • Prematurity
  • Hemophilia (due to hemarthroses)
  • Immunosuppression:
    • Chemotherapy
    • HIV
    • Sickle cell anemia
    • Diabetes
• Adults:
  • Age > 80 years
  • Chronic disease/immunosuppression:
    • Diabetes
    • HIV
  • Joint disease:
    • Rheumatoid arthritis
    • Osteoarthritis
    • Gout
  • Joint procedures:
    • Surgery
    • Intra-articular injections
    • Joint prosthesis
  • Skin infections or ulcers
  • IV drug use

Pathophysiology

• Invasion of the joint occurs through:
  • Hematogenous seeding (most common)
  • Direct inoculation of organisms into the joint
  • Extension from an adjacent infection
• Previously damaged joints are particularly susceptible to infection by way of:
  • Neovascularization
  • Dysfunctional cellular defenses
  • Absent basement membrane on the synovial membrane
• Progression of the disease:
  • Bacterial invasion → inflammation → release of cytokines and proteases
  • This response, plus bacterial toxins → destruction of: 
    • Articular cartilage
    • Synovium
    • Subchondral bone
  • Pannus formation occurs.
  • If a large effusion develops → impairment of the blood supply → aseptic necrosis

Clinical Presentation and Diagnosis

Clinical presentation

• Usually acute in onset
• Joint signs and symptoms:
  • Swelling and effusion
  • Warmth
  • Moderate-to-severe pain
  • Erythema
  • Restricted movement
  • Usually monoarticular, but 20% of cases may be oligo- or polyarticular
• Constitutional symptoms:
  • Fever
  • Fatigue
  • Tachycardia
• Commonly affected joints:
  • Knee (> 50% of cases)
  • Wrist
  • Ankle
  • Hip
  • Elbow
  • Axial joints (in IV drug users):
    • Sacroiliac
    • Sternoclavicular joint

Arthrocentesis

The diagnosis of septic arthritis is made with synovial fluid analysis.

• Should be attempted before antibiotics are given
• A positive Gram stain and/or culture confirms the diagnosis.
• A purulent aspirate gives a presumptive diagnosis:
  • WBC count > 50,000 cells/μL
  • Neutrophils predominance
• Nucleic acid amplification testing may be performed if N. gonorrhoeae is suspected.
• Include an analysis for crystals to rule out gout.

Laboratory evaluation

Laboratory studies that support the diagnosis:

• ↑ Erythrocyte sedimentation rate (ESR)
• ↑ CRP
• ↑ WBC count
• Blood cultures
• Cervical, urethra, rectal, or oropharyngeal swabs for nucleic acid amplification test if N. gonorrhoeae is suspected

Imaging

• Plain X-rays:
  • Joint-space narrowing or widening
  • Subchondral bony changes, osteopenia
  • Periarticular soft tissue swelling
  • Normal studies do not rule out septic arthritis.
• Ultrasound: 
  • Identification of a joint effusion
  • Can assist with aspiration of the effusion
• MRI: 
  • Sensitive for early identification of joint effusion
  • Evaluates the extent of bone and soft-tissue abnormalities
  • Assesses for associated osteomyelitis
  • Particularly helpful in evaluating sacroiliac and sternoclavicular joint infections

Management

Antibiotic therapy

Antibiotic selection is based on the initial Gram stain and tailored based on culture data.

• Empiric regimen if Gram stain is negative:
  • Vancomycin
  • 3rd- or 4th-generation cephalosporin
• Gram-positive cocci:
  • Empiric vancomycin
  • If cultures grow MSSA: 
    • Cefazolin
    • Nafcillin
    • Dicloxacillin
    • Flucloxacillin
    • Clindamycin or vancomycin if penicillin-allergic
  • If cultures grow MRSA: 
    • Vancomycin
    • Daptomycin
    • Linezolid
    • Clindamycin
• Gram-negative bacilli:
  • Empiric options:
    • 3rd- or 4th-generation cephalosporins
    • Aztreonam
  • For P. aeruginosa, add 1 of the following:
    • Fluoroquinolone
    • Gentamicin
• Gram-negative cocci:
  • Ceftriaxone (management of choice in N. gonorrhoeae infection)
  • Aminoglycosides

Duration of therapy depends on additional factors:

• With negative blood cultures:
  • 2 weeks of parenteral antibiotics
  • Additional 1–2 weeks of oral antibiotics
• With positive blood cultures: 4 weeks of parenteral antibiotics
• P. aeruginosa infection: 4–6 weeks

Surgical interventions

Joint drainage:

• Generally warranted in all patients
• Often requires repeated drainage
• Options:
  • Needle aspiration
  • Arthroscopic drainage
  • Arthrotomy (open surgery) is indicated when:
    • Repeated percutaneous drainage fails to control joint effusion
    • Joint is technically difficult to aspirate
    • Adjacent soft tissues are infected

Surgical debridement in patients with prosthesis:

• Debridement with preservation of prosthesis:
  • Infection occurs within 30 days of implantation.
  • Presentation within 3 weeks of symptom onset
  • No evidence of draining sinus tract
• Debridement with removal of prosthesis:
  • Prosthesis is removed and a joint spacer placed.
  • 6-week course of antibiotics
  • Eventual replacement with a new joint prosthesis

Differential Diagnosis

• Reactive arthritis: a seronegative, autoimmune spondyloarthropathy that is often precipitated by a GI or genitourinary infection. Patients present with an asymmetric oligoarthritis, enthesopathy, dactylitis, and/or sacroiliitis. The diagnosis is clinical, and a negative synovial Gram stain and culture will help rule out septic arthritis. Management includes NSAIDs, disease-modifying antirheumatic drugs (DMARDs), and treatment of an active infection.
• Gout arthritis: an arthritis due to precipitation of monosodium urate crystals in the joints. The condition is characterized by acute, painful, recurring, monoarticular arthritis. The most commonly involved joint is the 1st metatarsophalangeal joint. The diagnosis is made with identification of negatively birefringent, needle-shaped crystals in the synovial fluid, which differentiates gout from septic arthritis. Therapies include NSAIDs, colchicine, steroids, and uric acid reduction with allopurinol.
• Pseudogout: intra-articular calcium pyrophosphate deposition. The etiology is not clear. Patients present with acute flares of joint swelling, warmth, and pain. Pseudogout usually affects larger joints, such as the knee. Diagnosis is with identification of positively birefringent and rhomboid crystals in the synovial fluid, which differentiates pseudogout from septic arthritis. Management includes NSAIDs, corticosteroids, and colchicine.
• Osteoarthritis (OA): arthritis due to cartilage destruction and changes in the subchondral bone. Patients develop gradual joint pain, stiffness lasting < 30 minutes, and decreased range of motion. Physical exam may reveal crepitus with joint motion and osteophyte formation. The diagnosis is clinical. Synovial fluid will be non-inflammatory, which differentiates OA from septic arthritis. Management includes analgesics, glucocorticoid intra-articular injections, and surgery for advanced disease.
• Osteomyelitis: an infection of the bone most commonly caused by S. aureus. Patients present with pain, redness, and swelling of the affected site, and may have associated symptoms such as fever and chills. Laboratory values will demonstrate elevated WBC, CRP, and ESR in most cases. The most sensitive and specific imaging modality to diagnose osteomyelitis is MRI. Management requires long-term antibiotics and potential surgical debridement.
• Lyme disease: a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Patients with late disease may develop a migratory polyarthritis, particularly in large joints. An erythema migrans rash as well as neurologic, cardiac, and ocular manifestations may also be present. Synovial fluid analysis and serologic testing can confirm a Lyme infection and will differentiate the disease from septic arthritis. Antibiotic therapy is used for treatment.