Septic arthritis is an infection of the joint space caused by bacteria, fungi, mycobacteria, and viruses. Septic arthritis typically involves large joints such as the knee, hip, and shoulder, though any joint can be affected. The knee is most commonly affected in adults, while the hip is most commonly affected in children. The bacteria responsible for septic arthritis vary by the age of the patient, though Staphylococcus aureus is a common pathogen across all age groups. Septic arthritis can lead to permanent joint damage unless treated expeditiously with joint irrigation and appropriate antibiotic treatment.

Structure and Function

A microbe can infiltrate the joint via three methods: hematogenous spread, contiguous spread, or direct inoculation. Hematogenous spread is the most common mechanism: because the articular capsule lacks a basement membrane, the joint space is susceptible to invasion from organisms in the bloodstream. Contiguous spread occurs when a nearby infection, such as osteomyelitis in an adjacent bone or cellulitis of the skin overlying the joint (Figure 1), reaches the joint. Direct inoculation of the joint space can occur either through trauma or iatrogenic causes, such as surgeries or injections.

When the body senses the infection, it mounts an acute inflammatory response. Local macrophages and dendritic cells are activated. These cells release molecular signals that increase blood vessel permeability and recruit neutrophils. Neutrophils then release proteolytic enzymes that kill the invading organisms, but these enzymes are also toxic to the native articular cartilage. Thus, treatment involves removing the joint fluid as well as directing antibiotics against the offending organisms.

The bacteria responsible for septic arthritis vary by the age of the patient. In children under one month of age, the common causes are Staphylococcus aureus, Group B streptococcus, Gram-negative organisms, and Streptococcus pneumoniae. In children between one month and three years of age, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Kingella kingae, and Haemophilus influenza type B are seen. These bacteria, with the exception of Kingella kingae, are also seen in children older than three years of age. In adolescents, the common causes are Staphylococcus aureus, Neisseria gonorrhoeae, Streptococcus pneumoniae, and Streptococcus pyogenes.

Among adults, the most common organism is Staphylococcus aureus, which accounts for the majority of cases. Neisseria gonorrhea accounts for ~20% of cases and Gram-negative bacilli such as E. coli, Klebsiella, and Enterobacter account for another 15%.

Patient Presentation

In pediatric septic arthritis, patients typically present with acute onset guarding of a joint. Initially, the pain is often poorly localized. A history of mild trauma is common but might be coincidental. If the lower extremity is involved, patients often have a limp or will refuse to bear weight. If the upper extremity is involved, patients might refuse to use that extremity. Patients typically also have systemic symptoms, such as malaise, fever, and poor appetite.

On physical exam, the child often appears ill and will tend to hold the affected joint in a position to accommodate joint distention. Patients with septic arthritis of the hip tend to hold the hip in a flexed, abducted, and externally rotated position; if the knee is involved, the joint is held in a slightly flexed position. Children are typically apprehensive and resist attempts to examine the affected extremity. Any movement of the joint is typically painful. The joint is often tender to palpation.

Septic arthritis in the adult typically presents as an acute condition of a single joint (monoarthropathy), usually the knee, with joint pain, swelling, warmth, and restricted movement (Figure 2).

Adults suffering from septic arthritis also tend to hold the joint in a rigid position that maximizes the joint space, thereby minimizing pressure from the effusion. Passive motion by the examiner will be very painful.

Fever can be present in septic arthritis, especially if the mode of infection is hematogenous seeding, but can be absent in up to 40% of cases. Thus, normal temperature does not rule out the presence of septic arthritis.

Polyarticular infections occur in 20% of cases of septic arthritis. Such cases of septic arthritis involving multiple joints are more commonly seen in patients with rheumatoid arthritis or underlying immune compromise.

Objective Evidence

Objective evidence related to the diagnosis of septic arthritis comes from three sources: blood tests; synovial fluid aspiration and examination; and medical imaging.

Inflammatory markers such as the peripheral white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level can be increased in septic arthritis but are nonspecific. These values can also be normal early in the disease course.

Blood cultures are positive in ~25% of cases of septic arthritis. Although blood cultures neither confirm nor exclude the diagnosis of septic arthritis, positive results can be used to confirm the infectious pathogen and tailor antimicrobial therapy.

Joints that are suspected of having an infection should be aspirated (Figure 3). Removing the joint fluid can provide pain relief by dissipating the pressure within the joint space. However, the main purposes of aspiration are removing the WBCs that can damage the cartilage and providing a specimen for definitive diagnosis. The synovial fluid aspirate of a septic joint is often yellow and turbid, though the appearance of the fluid is not diagnostic. For that reason, laboratory analysis is routine.

The gold standard for diagnosing septic arthritis is a positive bacterial culture of synovial fluid obtained from a joint aspiration. However, culture results may not be known for 24 to 48 hours, and waiting that long to treat can be harmful. Thus, information that could be obtained immediately – namely, the number of WBCs per microliter – is used as a proxy.

A common clinical decision rule is that a synovial WBC count of 50,000 cells should be treated as if an active infection were present. However, there is an overlap in the distributions of cell counts seen in people with infection and those without infection (Figure 4). Thus, there is an inevitable sensitivity-specificity trade-off.

Although an elevated WBC count in the synovial fluid suggests septic arthritis, it can also be seen in other inflammatory conditions such as rheumatoid arthritis. Accordingly, it may be helpful to examine the fraction of WBCs that are polymorphonuclear leukocytes. When a borderline WBC count is composed of more than 90% polymorphonuclear leukocytes, it is highly likely that an infection is present.

The Kocher criteria can be used to assist in diagnosing pediatric septic arthritis of the hip. The four criteria are 1) fever over 38.5 degrees Celsius, 2) inability to bear weight on the affected extremity, 3) ESR greater than 40 mm/hr, and 4) WBC count greater than 12,000 cells/uL. If a patient has three of these factors, the probability of septic arthritis is more than 90%. If all four factors are present, the diagnosis of septic arthritis is a virtual certainty.

Analyzing the fluid for crystals can rule out crystal arthropathy, though a joint with gout or pseudogout can be infected as well. Gram staining and culturing the fluid will aid in tailoring the appropriate antimicrobial therapy. Gram stains are positive in ~70% of cases of nongonococcal septic arthritis. Cultures may be negative in the setting of recent antibiotic use or with certain pathogens such as Neisseria gonorrhoeae.

Radiographic findings for septic arthritis are nonspecific. As septic arthritis progresses and causes more damage and inflammation, X-rays will reveal an enlarged joint space and joint effusion. Later in the course, plain X-rays may show juxta-articular osteopenia from hyperemia, joint space narrowing from cartilage destruction, and destruction of subchondral bone.

Ultrasound and MRI are useful for evaluating the presence of joint effusions (Figures 5 and 6).

Epidemiology

The overall incidence of septic arthritis ranges from 4 to 29 cases per 100,000 persons around the world. The incidence in the United States is ~8 cases per 100,000 persons. While people of any age can have septic arthritis, about half of the cases in adults occur in individuals 65 years of age or older.

Differential Diagnosis

In children with suspected septic arthritis, other diagnoses to consider include transient synovitis, hemarthrosis, inflammatory diseases, Legg-Calve-Perthes disease, and neoplastic processes. Hemarthrosis can occur secondary to hemophilia or trauma. Other infectious etiologies to consider include osteomyelitis, pyomyositis, and Lyme disease. Inflammatory diseases to consider include juvenile idiopathic arthritis, reactive arthritis, and rheumatic fever. Neoplastic processes to consider include leukemia and pigmented villonodular synovitis (PVNS).

Acute monoarthropathy in the adult has a broad differential. These can be split into infectious and noninfectious causes. Infectious causes include septic arthritis, septic bursitis, and overlying cellulitis. It is important to discern if the infection is intra-articular before proceeding with joint aspiration. Sticking a needle through a cellulitis into a joint and causing septic arthritis is considered poor form, to say the least.

Non-infectious causes of acute monoarthropathy include crystal arthropathy (gout and pseudogout), reactive arthritis, rheumatoid arthritis, and osteoarthritis. Joint aspiration is required to discern septic arthritis from a crystal arthropathy. Specific tests for Lyme disease are helpful after first taking a careful history.

Red Flags

Acute onset pain and reluctance to move a joint is a red flag finding suggesting septic arthritis.

Any recent history of invasive procedures or trauma near the affected joint, IV drug use, or an immunosuppressed state raises suspicion for septic arthritis as well.

Treatment Options and Outcomes

Septic arthritis should be treated urgently. The treatment for septic arthritis of any joint is drainage of the fluid and initiation of antibiotic coverage. One treatment approach is surgical: joint irrigation and drainage via arthroscopy (see Figure 7) or (less commonly) open arthrotomy. Another option is drainage via serial needle aspirations. Both approaches are demonstrably effective.

Empiric antibiotics need to be started after joint aspiration is completed. Vancomycin provides broad coverage for gram positive bacteria. If the gram negative bacteria are suspected or identified on gram stain, a 3rd or 4th generation cephalosporin should be added. If the patient has a history of IV drug abuse and Pseudomonas coverage is needed, a 3rd or 4th generation cephalosporin with an aminoglycoside like gentamicin should be administered. Antibiotics can be tailored to a specific pathogen if and when one is identified on synovial fluid cultures.

Serial synovial fluid analyses can be monitored for WBC counts reverting to normal; additional cultures can be obtained from that fluid as well.

The correct duration of antibiotic treatment is not known with certainty. Many physicians treat septic arthritis with intravenous antibiotics for 2 weeks followed by another 2 weeks of oral therapy. Physical therapy is often recommended to regain strength and full range of motion.

Outcomes from treatment depend on host factors, the offending organism, and timing. About 50% of normal hosts will completely recover. Patients with underlying joint disease develop functional impairment in about 1/3rd of cases. In-hospital mortality rates of 15% or greater have been cited, though it may be that the septic arthritis is simply a manifestation of terminal decline (i.e., not the true cause of the patient’s demise).

Risk Factors and Prevention

Risks for septic arthritis include age >80 years old, diabetes mellitus, immunosuppressed states, immunosuppressive medications, underlying arthritis but especially rheumatoid arthritis, recent exposure of the joint from trauma or surgery, and other infections, either nearby (e.g., cellulitis and osteomyelitis) or distal. As seen, very few of these factors are “modifiable,” and thus the true role of prevention is to prevent complications of septic arthritis by timely diagnosis and treatment.

Miscellany

Septic arthritis in a joint with a prior arthroplasty is of special concern because unless the infection is caught early, it is extremely difficult to eradicate the bacteria and prevent failure of the arthroplasty. Most cases of prosthetic joint infections found within the first weeks after surgery are caused by seeding at the time of implantation. Late cases are usually secondary to hematogenous spread from oral, urinary tract or visceral infections. (This topic is beyond the scope of this volume but the interested reader might wish to consult an open-access review such as this one: Li, C. et al. Twenty common errors in the diagnosis and treatment of periprosthetic joint infection. International Orthopaedics (SICOT) 44, 3–14 (2020). https://doi.org/10.1007/s00264-019-04426-7.)

Staphylococcus aureus is the most common organism causing septic arthritis. Some elements of the patient’s history can suggest other organisms, as shown in the table.

Key Terms

Septic arthritis, joint aspiration, joint irrigation

Skills

Recognize signs and symptoms of septic arthritis. Perform joint aspiration using sterile technique.