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Am Fam Physician. 2021;104(6):589-597

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Septic arthritis must be considered and promptly diagnosed in any patient presenting with acute atraumatic joint pain, swelling, and fever. Risk factors for septic arthritis include age older than 80 years, diabetes mellitus, rheumatoid arthritis, recent joint surgery, hip or knee prosthesis, skin infection, and immunosuppressive medication use. A delay in diagnosis and treatment can result in permanent morbidity and mortality. Physical examination findings and serum markers, including erythrocyte sedimentation rate and C-reactive protein, are helpful in the diagnosis but are nonspecific. Synovial fluid studies are required to confirm the diagnosis. History and Gram stain aid in determining initial antibiotic selection. Staphylococcus aureus is the most common pathogen isolated in septic arthritis; however, other bacteria, viruses, fungi, and mycobacterium can cause the disease. After synovial fluid has been obtained, empiric antibiotic therapy should be initiated if there is clinical concern for septic arthritis. Oral antibiotics can be given in most cases because they are not inferior to intravenous therapy. Total duration of therapy ranges from two to six weeks; however, certain infections require longer courses. Consideration for microorganisms such as Neisseria gonorrhoeae, Borrelia burgdorferi, and fungal infections should be based on history findings and laboratory results.

Septic arthritis should be considered in adults presenting with acute monoarticular arthritis. A delay in diagnosis and treatment of septic arthritis can lead to permanent morbidity and mortality. Subcartilaginous bone loss, cartilage destruction, and permanent joint dysfunction can occur if appropriate antibiotic therapy is not initiated within 24 to 48 hours of onset.1 The reported incidence of septic arthritis is four to 29 cases per 100,000 person-years, and risk increases with age, use of immunosuppressive medications, and lower socioeconomic status.2

Intra-articular infection is typically monoarticular, with up to 20% of cases occurring in multiple joints (oligoarticular [also called polyarticular]).1,3 A joint is most commonly infected hematogenously from bacteremia. Staphylococcus aureus and Streptococcus species are the most common causes. Septic arthritis is diagnosed through laboratory testing, particularly synovial fluid studies.

Diagnosis

HISTORY AND CLINICAL PRESENTATION

The presentation of septic arthritis may vary based on pathogen, underlying medical conditions, or exposures (Table 1).1,2,47 Septic arthritis may present similarly to other types of arthritis. More than 50% of patients with septic arthritis have a history of joint swelling, joint pain, and fever. Sweats or rigors are less common. Native joint infections most commonly occur in the knee, followed by the hip, shoulder, ankle, elbow, and wrist.1 Patients with septic arthritis may present with an acutely painful atraumatic joint, which should be differentiated from other causes of monoarticular joint pain (Figure 1810 and Table 21 ).

Clinical history or exposureJoint involvementPathogen
Cleaning fish tankSmall joints (fingers, wrists)Mycobacterium marinum
Dog or cat biteSmall joints (fingers, toes)Capnocytophaga species, Pasteurella multocida
Exposure to soil or dust containing decomposed wood (North Central and Southern United States)Monoarticular; knee, ankle, or elbowBlastomyces dermatitidis
Ingestion of unpasteurized dairy productsMonoarticular, sacroiliac jointBrucella species
Intravenous drug abuseAxial joints, such as sternoclavicular or sacroiliac jointPseudomonas aeruginosa, Staphylococcus aureus
Nail through shoeFootP. aeruginosa
Older ageIncreased risk of gram-negative infections
Prosthetic jointAny prosthetic jointCoagulase-negative staphylococci, Pseudomonas species, Pneumococcus species
Sexually activeTenosynovial component in hands, wrists, or anklesNeisseria gonorrhoeae
Soil exposure/gardeningMonoarticular; knee, hand, or wristNocardia species, Pantoea agglomerans, Sporothrix schenckii
Southwestern United States, Central and South America (primary respiratory illness)KneeCoccidioides immitis
Underlying medical conditions
 Diabetes mellitus or immunocompromiseIncreased risk of fungal infection (most commonly Candida), Pseudomonas, and Escherichia coli
 GoutIncreased risk of Pseudomonas and E. coli
 Rheumatoid arthritisOligoarticular (also called polyarticular)Increased risk of fungal (most commonly Candida) and pneumococcus infections
 Systemic lupus erythematosus (particularly with functional hyposplenism)N. gonorrhoeae, Proteus species, Salmonella species
 Terminal complement deficiencyTenosynovial component in hands, wrists, or anklesN. gonorrhoeae
DiagnosisEtiology
Crystal-induced arthritisCalcium oxalate, cholesterol, gout, hydroxyapatite crystals, pseudogout
Infectious arthritisBacteria, fungi, mycobacteria, spirochetes, viruses
Inflammatory arthritisBehçet syndrome,* rheumatoid arthritis,* sarcoidosis, seronegative spondyloarthropathy (e.g., ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease), Still disease,* systemic lupus erythematosus,* systemic vasculitis*
OsteoarthritisErosive/inflammatory variants*
Systemic infectionBacterial endocarditis, HIV infection
TumorMetastasis, pigmented villonodular synovitis
OtherAmyloidosis, avascular necrosis, clotting disorders/anti-coagulant therapy, familial Mediterranean fever,* foreign body, fracture, hemarthrosis, hyperlipoproteinemia,* meniscal tear

Oligoarticular septic arthritis is more likely to present with symptoms of systemic infection and more commonly affects the shoulder, wrist, and elbow.11 Bacteremia is especially common with septic arthritis of the shoulder.

RISK FACTORS

Risk factors for septic arthritis are listed in Table 3.1,11 Patients with rheumatoid arthritis and a flare-up in one or multiple joints are at particularly high risk. In one study, the incidence of septic arthritis was 1.8 per 1,000 patient-years in those treated with nonbiologic disease-modifying antirheumatic drugs vs. 4.2 per 1,000 patient-years in those treated with anti–tumor necrosis factor therapy.12 People who smoke tobacco also have an increased risk of septic arthritis.2

Contiguous spread
Skin infection, cutaneous ulceration
Direct inoculation
Previous intra-articular injection
Prosthetic joint (within two years)
Recent joint surgery
Hematogenous spread
Diabetes mellitus
HIV infection
Immunosuppressive medication use
Intravenous drug abuse
Osteoarthritis
Other causes of sepsis
Prosthetic joint (more than two years)
Rheumatoid arthritis
Sexual activity (gonococcal arthritis)
Other
Age older than 80 years
Smoking

PHYSICAL EXAMINATION

The physical examination of patients with septic arthritis almost always reveals a severely painful joint with motion, often including an obvious effusion. The presentation is typically more subtle in those with periprosthetic joint infections, small joint infections, atypical infections (e.g., fungal, Lyme disease, tuberculosis), or immunosuppression. An overlying skin infection can be the source of pain or the entry point of the intra-articular infection.

LABORATORY EVALUATION

Serum markers may be helpful in evaluating for septic arthritis but are not diagnostic. A 2011 study showed that serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) level are each more than 90% sensitive for septic arthritis when low cutoffs are used (98% for ESR of 10 mm per hour or greater, 94% for ESR of 15 mm per hour or greater, and 92% for CRP of 2.0 mg per dL [20 mg per L] or greater), which is helpful in ruling out septic arthritis.8 A 2017 meta-analysis showed that with a cutoff of 0.5 ng per mL or greater, procalcitonin has a higher specificity than CRP (95% CI, 0.87 to 0.98; positive likelihood ratio = 10.97).13 Blood cultures should be considered when bacteremia or fungemia is suspected.

Analysis of synovial fluid obtained via arthrocentesis is necessary to differentiate septic arthritis from other forms of arthritis and to determine the causative pathogen.1,4 Synovial fluid analysis should include Gram stain, aerobic and anaerobic cultures, and white blood cell count with differential (Table 41,1416).

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