A 54-year-old woman with a history of rheumatoid arthritis presents with a two-day history of swelling in multiple joints, fever, and pain. She has significant difficulty with active or passive range of motion at the affected joints because of severe pain. She denies any recent trauma, rash, headache, cough, or urinary complaints. The patient takes a daily immunosupressive regimen for her arthritis.
What condition are you concerned about, and how would you diagnose this?
Diagnosis: Septic Arthritis
Septic arthritis is a pathologic infection of joint synovial fluid that can cause destruction of local joint tissues, necessitating joint replacement and rarely but devastatingly limb amputation if left untreated. Numerous organisms, including fungi, bacteria, spirochetes, and mycobacteria, can infect synovial fluid, but bacterial infections are the most destructive. The prevalence of bacterial septic arthritis in patients with acutely painful joints is estimated to be as high as 25 percent, with gonococcal arthritis the most common infectious etiology. (Rheum Dis Clin North Am 1993;19:363.) Local infiltration of pathogenic organisms into the synovium creates an inflammatory cascade of cells and cytokines that destroys local tissues and cartilage. Subsequent development of a joint effusion can cause local pressure necrosis and further joint damage.
Joint infections are most commonly the result of hematogenous spread (Epidemiol Infect 1996;117: 423), but can be the result of inoculation from local cellulitis, infection, direct joint seeding during orthopedic surgery or local trauma, or rarely extension of infected bone into the joint. Clinicians should assume anyone with bacteremia, sepsis, or endocarditis and joint pain has septic arthritis until proven otherwise.
Risk factors include immunocompromise, old or young age, intravenous drug use, indwelling catheters, joint surgery, skin infection, and previous history of arthritis. (Arthritis Rheum 1997;40:884.) A 2007 study reported the risks to be age over 80 (+likelihood ratio [LR] 3.5), diabetes mellitus (+LR 2.7), rheumatoid arthritis (+LR 2.5), prosthetic joint (+LR 3.1), recent joint surgery (+LR 6.9), skin infection (+LR 2.8), and joint prosthesis (+LR 15.0). (Arthritis Rheum 1995;38:1819.) In immunocompetent adults, Staphylococcus aureus is the most common bacterial etiology (N Engl J Med 1985; 312:764), with Strepotococcal species and Neisseria gonorrhea as other common etiologies.
ED patients with septic joints classically present with fever and monoarthritis, including a warm, swollen, erythematous joint with decreased active and passive range of motion. A history of joint pain (85%), joint swelling (78%), and fever (50%) are the only findings consistently occurring in more than half of patients. (JAMA 2007;297:1478.) More than half involve the knee, but others involve the hip, wrist, ankle, and sternoclavicular and pubis symphysis joints. Polyarthritis can occur, but is more common in those with a history of connective tissue disease or sepsis.
The differential diagnosis of a septic joint is fairly circumscribed and includes gout, pseudogout, trauma, hemarthrosis, malignancy, and Lyme arthritis, among others.
Radiographs are usually nonspecfic and unhelpful in diagnosing septic arthritis. (Skeletal Radiol 2001; 30:565.) Diagnosis is made by identifying the pathogenic organism from synovial fluid. Many resources describe arthrocentesis techniques for various joints (New Engl J Med 2006;354:e19), with some literature supporting ultrasound to aid in collection. (J Emerg Med 2008 Dec 4. Epub ahead of print.)
If joint fluid cannot be obtained by arthrocentesis, computerized tomography and fluoroscopy-guided techniques may be used. Arthrocentesis should not be performed through cellulitic skin, with concern for joint seeding, but the risk of an undiagnosed septic arthritis needs to be considered. Prosthetic joint infections are a concern; infection rates are as low as two percent for most new joint replacements but as high as 20 percent in late-onset infections. Diagnosing and managing a suspected infection should be done in consultation with an orthopedist.
Laboratory evaluation of synovial fluid should include gram stain, culture, crystal identification, and leukocyte count with differential. As little as one drop of fresh fluid transported expeditiously to the laboratory may be sufficient for a cell count and differential. ESR (>30mm/h; +LR 1.3), C-reactive protein (>100mg/L; +LR 1.6), and serum white blood cell count have a limited role in diagnosis because of poor sensitivity. (Am J Emerg Med 1997;15:626; Scand J Infect Dis 1998;30:591.)
Normal joint fluid is typically clear, highly viscous (positive string sign: fluid dripped from height will have string-like projection as it falls), and acellular, with glucose levels similar to serum. Septic fluid is typically cloudy, yellow-tinged, and has greater than 100,000 WBC/mm3 and a 75% or greater polymorphonuclear cell count (PMNs). Partially treated infections, low-virulence organisms, and infections in immuncompromised patients may not appear as such. It can be difficult to differentiate septic joint aspirate from inflammatory process. Inflammatory arthritic fluid tends to be less cloudy, have a low viscocity, and 10,000 WBC/mm3 or less with 50% or greater PMNs. Aspirates with greater than 100,000 WBC/mm3 can be seen with some severe noninfected inflammatory arthritic flares. Hemorrhagic fluid aspiration is worrisome for trauma, which may be minor in patients with hemophilia or on anticoagulants, and classically has a bloody, rust, or red-tinged appearance.
Unfortunately, the sensitivity and specificity of gram stain to diagnose a septic joint is unknown, and may be as low as 10 percent (Rheum Dis Clin North Am 1994;20:503) or as high as 50 percent in patients with a septic arthritis. (JAMA 2007;297:1478.) Culture results are not always helpful either, with a positive culture rate of less than 50 percent in known gonococcal arthritis. (Arch Intern Med 1994;154:2690.) False-negative cultures also can occur in patients previously on antibiotics.
As the synovial fluid WBC count increases, so does the LR: <25,000/ microL (+LR 0.32), greater than or equal to 25,000/microL (+LR 2.9), greater than 50,000/microL (+LR 7.7), and greater than 100,000/microL (+LR 28.0). A 90% PMN count suggests septic arthritis (+LR of 3.4) while less than 90% significantly decreases the likelihood (+LR 0.34). (JAMA 2007; 297:1478.) One emergency medicine study found that more than a third of adult ED patients with septic arthritis had joint WBCs less than 50,000 cells/mm3, and they concluded that laboratory tests (including WBC, joint WBC and ESR) do not rule out septic arthritis with accuracy. (Acad Emerg Med 2004;11:276.)
If septic arthritis is suspected or confirmed, antibiotic therapy should be targeted at the suspected or known pathogen. The ideal duration of antibiotic therapy is not currently known, but some recommend prolonged intravenous and then oral antibiotic treatment (some as long as one month). Unfortunately, the in-hospital mortality rate for septic arthritis is still seven to 15 percent. (JAMA 2007;297:1478.) This patient was admitted to the hospital for intravenous antibiotic therapy, and was ultimately found to have septic arthritis secondary to E. coli.