Septic Arthritis

Etiology

Etiology in Children

Arthritis or inflammation of the joint has multiple etiologies in the pediatric age group. Staphylococcus aureus is the most common bacterial pathogen overall. Some etiologic agents are associated with specific age groups and underlying medical conditions.  Kingella kingae is the most common gram-negative bacterial cause in children younger than 2 to 3 years. Group B Streptococcus, Staphylococcus aureus, Neisseria gonorrhea, and gram-negative Bacilli are common among neonates. Neisseria gonorrhea is a concern in sexually active adolescents.  Salmonella species infection is associated with sickle cell disease. Patients on prolonged antibiotic therapy are at risk for fungal infections. Puncture wounds and injection drug use are associated with joint infection due to Pseudomonas aeruginosa. The hip joint is most commonly affected in children.

Etiology in Adults

Staphylococcus aureus is the most common infecting organism in adults. Streptococcus pneumonia is less common, but still a significant source of infection in adults. Other special circumstances are as already described as above (Salmonella in patients with sickle cell, and Pseudomonas in trauma/puncture wounds). In young sexually active patients, nontraumatic acute monoarthritis is most frequently caused by Neisseria gonorrhea. In high-risk patients, Neisseria gonorrhea should be cultured from other sites such as the oropharynx, vagina, cervix, urethra or anus as the organism grows poorly from cultured synovial fluid.[3] Fungal and mycobacterial organisms present insidiously and may be more difficult to diagnose. The acid-fast smear of synovial fluid is often negative, but a synovial biopsy is positive in 95% of cases. The knee is the most commonly affected joint in adults followed by the hip.

Polymicrobial joint infections occur in about 5% of patients as a result of trauma or abdominal infection. Infection of the sternoclavicular and sacroiliac joint often occur in patients with IV drug abuse and usually involve serratia and pseudomonas. Individuals with leukemia are highly susceptible to Aeromonas infections.

Joints previously damaged especially in patients with rheumatoid arthritis are highly susceptible to infection. The organisms damage the articular cartilage along the lateral edges of the joint. Effusions are common and often associated with pain.

Epidemiology

The incidence of septic arthritis is between 2 to 6 cases per 100,000 people but varies based on the presence of risk factors.[4] Septic arthritis is more common in children than in adults. The incidence of septic arthritis peaks between ages 2 and 3 years and has a male predominance (2:1). Subgroups of children at high risk include neonates, hemophiliacs with hemarthroses, immunocompromised (e.g., sickle cell anemia, human immunodeficiency virus infection), and those treated with chemotherapy. Risk factors in adults include age older than 80, diabetes mellitus, rheumatoid arthritis, recent joint surgery, joint prosthesis, previous intra-articular injection, skin infections and cutaneous ulcers, Human immunodeficiency virus, osteoarthritis, sexual activity (especially in cases of suspected gonococcal septic arthritis), other causes of sepsis.[5][6]

Pathophysiology

The highly vascularized joint synovium lacks a limiting basement membrane so is prone to infection via hematogenous seeding from systemic infection. Septic arthritis may also result from direct injury, puncture wounds, and intra-articular injections. Contiguous spread from adjacent osteomyelitis may occur. The hip and shoulder are vulnerable to contiguous spread. Septic arthritis occurs when there is a bacterial invasion of the synovium and joint space followed by an inflammatory process. Inflammatory cytokines and proteases mediate joint destruction. Other factors which play a role in joint damage are bacterial toxins (based on animal models[7]) and microbial surface components like staphylococcal adhesins which promote the binding of the bacteria to intra-articular proteins.[4][5][6]

Prosthetic joint infections are classified into:

1. Early within 3 months of implantation
2. Delayed within 3-24 months of surgery
3. Late: occurring after 24 months

Most early prosthetic joint infections are caused by staphylococcus, whereas delayed cases are due to gram negatives and coagulase-negative staphylococcus. Late cases are usually secondary to hematogenous spread from various foci.

History and Physical

Septic arthritis classically presents with acute onset monoarticular joint pain, fever, swelling, and a reluctance or refusal to move the affected joint. Fever may be present in 40% to 60% of cases but is a nonspecific finding.[4] Lower extremities joints (hips, knees, and ankles) are affected in most cases of septic arthritis, with the knee being the most commonly affected joint in adults. 20% of cases are oligoarticular especially in the setting of severe sepsis, immune compromise, rheumatoid arthritis or multiple comorbid conditions.[4] Involvement of less common joints such as the sacroiliac or sternoclavicular joint occurs in injection drug users. Adults with suspected gonococcal arthritis are usually young, healthy and sexually active. On physical examination, they may have dermatitis, tenosynovitis, non-erosive arthritis and a migratory pattern of arthritis.

Children with septic arthritis may present with local symptoms only or both local and systemic symptoms.

Local symptoms:  Pain, joint swelling, warmth, limited range of motion, limp, refusal to use or move the affected joint (pseudoparalysis)

Systemic symptoms: Ill appearance, fever, tachycardia, fussiness/irritability, decreased appetite

Physical

The knee is the most common joint involved in septic arthritis, followed by the hip, shoulder, and ankle. Effusions are common on examination. The range of motion is limited and palpation may be associated with pain. Most staphylococcal infections are associated with monoarticular involvement but Neisseria often involves multiple joints.  Group B streptococci often involves the sternoclavicular and sacroiliac joints. Most prosthetic joint infections will have a draining sinus.

Evaluation

The evaluation of suspected septic arthritis includes arthrocentesis with synovial fluid analysis, laboratory and imaging studies.

Laboratory Studies

The most useful diagnostic laboratory test for identifying septic arthritis is an evaluation of the synovial fluid from the affected joint (culture, Gram stain, crystals analysis, white blood cell count with differential). Synovial fluid with a white blood cell (WBC) count greater than 50,000 and 90% neutrophil predominance suggests a bacterial source.[5] Identification of a bacterial organism in the synovial fluid confirms the diagnosis. Other useful laboratory tests include a complete blood count, an erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and blood cultures. The peripheral blood WBC count is typically elevated with a left shift. An elevated ESR and CRP support the diagnosis but are not definitive. A low synovial fluid WBC count may occur in peripheral leukopenia, early infection, disseminated gonococcal arthritis, and the presence of joint prosthesis.[3][4][5][6]

In prosthetic joint infections, synovial fluid WBC count of 1100 with a neutrophil differential of 64% suggests septic arthritis.[6]

Two sets of blood cultures should be obtained to rule out bacteremia. If Neisseria is suspected, one should obtain cultures from the cervix, rectum, and throat.

Imaging Studies

Plain radiographs may reveal widened joint spaces, bulging of the soft tissues, or subchondral bony changes (late finding). A normal plain radiograph does not rule out septic arthritis. Ultrasonography is useful in identifying and quantifying the joint effusion as well as aiding in needle aspiration of the joint.[4][6]

MRI is sensitive for early detection of joint fluid and may reveal abnormalities in surrounding soft tissue and bone, and delineate the extent of cartilaginous involvement.

Bone scans are not specific and cannot differentiate infections from a sterile process. However, they are useful when evaluating localized infection of the sacroiliac or hip joint.

Treatment / Management

Treatment of septic arthritis comprises antimicrobial therapy and joint fluid drainage (arthrotomy, arthroscopy, or daily needle aspiration). Empiric intravenous antimicrobial therapy should be initiated promptly after joint aspiration is complete and cultures obtained. Empiric antibiotic coverage includes antistaphylococcal coverage (nafcillin, oxacillin, or vancomycin) for all age and risk categories. Empiric antibiotics for nongonococcal septic arthritis usually involves the use of intravenous vancomycin directed against gram-positive organisms especially if there is a suspicion of MRSA based on community and institutional data. If the patient is immunocompromised, abuses intravenous drugs or the gram stain is negative, then a third-generation cephalosporin like ceftriaxone, ceftazidime or cefotaxime should be added for the additional gram-negative coverage.[4][6] Age, risk factors, and gram stain result should direct additional antibiotics (e.g., a third-generation cephalosporin for suspected Salmonella or N. gonorrhea). Blood and synovial fluid cultures and sensitivities should direct prolonged antimicrobial treatment. Early involvement by an orthopedic surgeon is essential. The procedure used to drain joint fluid depends on multiple factors and is determined by the orthopedic surgeon.

Nongonococcal septic arthritis is usually treated with intravenous antibiotics for 2 weeks followed by another 1 to 2 weeks of oral antibiotic therapy for a total duration of three to four weeks. Longer antibiotic therapy for 4 to 6 weeks may be reasonable in cases of Pseudomonas aeruginosa. Gonococcal arthritis responds well to intravenous ceftriaxone which is continued for 24 to 48 hours after clinical improvement then transitioned to oral therapy for the remainder of the treatment.[4][6]

If no improvement is seen within 5-6 days, the joint should be re-aspirated and one should rule out Lyme disease. One should also consider the presence of fungi or reactive arthritis. Imaging studies are needed in such scenarios to rule out osteomyelitis.

Immobilization of the joint is not needed after 2-3 days. Aggressive physical therapy is necessary to restore joint function and prevent muscle atrophy.

Prosthetic joint infection often requires aggressive debridement and/or removal of the prosthesis. The new joint is then replaced with cement which is impregnated with antibiotics.

Differential Diagnosis

Differential diagnosis of acute monoarticular arthritis include:

1. Infection: Bacterial, fungal, viral, spirochete, mycoplasma
2. Crystal-induced arthropathies: Acute gout, pseudogout, calcium oxalate, cholesterol, hydroxyapatite crystals
3. Osteoarthritis
4. Intra-articular injury: Fracture, meniscal tear, osteonecrosis, foreign body, plant thorn synovitis
5. Inflammatory arthritis: Rheumatoid arthritis, Bechet syndrome, seronegative spondyloarthropathies such as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, inflammatory bowel disease-related arthritis; Sarcoid, systemic Lupus erythematosus, Still disease
6. Systemic infection: Bacterial endocarditis, human immunodeficiency virus, Lyme arthritis
7. Tumor: Metastasis, pigmented villonodular synovitis
8. Other: Hemarthrosis, clotting disorders or anticoagulant therapy, neuropathic arthropathy, dialysis-related amyloidosis, avascular necrosis[6][5]

Prognosis

Despite antibiotic use, there is a 7% to 15% mortality rate for in-hospital septic arthritis.[5] Morbidity from septic arthritis occurs in one-third of patients. Both morbidity and mortality increase with patient age, comorbid conditions including pre-existing joint disease, and prior synthetic intra-articular material. This underscores the need for a high index of suspicion, early diagnosis and prompt treatment for septic arthritis especially in patients with known predisposing risk factors and comorbid conditions. Infection with Neisseria is rarely associated with death, whereas infection caused by staphylococcus can carry a mortality rate in excess of 50%.

Complications

Complications of septic arthritis include:

1. Osteomyelitis
2. Chronic pain 
3. Osteonecrosis
4. Leg length discrepancies
5. Sepsis
6. Death