Etiology

Isolation of a bacterial source of osteomyelitis occurs in 50% to 80% of patients when both blood and bone are cultured. The bacteria responsible for osteomyelitis in children vary by age and underlying condition (see Figure 88-1). Staphylococcus aureus is the most common pathogen in any age group (70%-90% of cases), with community-acquired methicillin-resistant S. aureus (CA-MRSA) becoming more prevalent in recent years. In infants younger than 2 months of age, group B streptococci and gram-negative enteric bacteria are seen in addition to S. aureus. In children younger than 5 years of age, S. aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Kingella kingae are leading causes of osteomyelitis. Children older than 5 years of age are most commonly infected by S. aureus or S. pyogenes. Neisseria gonorrhoeae may be the etiologic agent in sexually active adolescents.

Approximately 10% of cases of acute hematogenous osteomyelitis are caused by S. pyogenes, a pathogen that tends to cause higher fever and white blood cell (WBC) count than S. aureus. An upper respiratory tract infection often precedes osteomyelitis with K. kingae, and this organism has been associated with outbreaks at daycare centers. Joint involvement is more common with S. pneumoniae than with S. aureus and S. pyogenes, perhaps because children with osteomyelitis caused by S. pneumoniae tend to be younger.

After introduction of the Haemophilus influenzae type b (Hib) conjugate vaccine, the frequency of osteomyelitis caused by this organism has significantly decreased. Actinomyces spp. have been isolated in facial and cervical osteomyelitis. Mixed flora, including Pseudomonas spp., S. aureus, and anaerobes, are seen in osteomyelitis that occurs after a puncture wound to the foot through sneakers. Salmonella spp. are an important cause of osteomyelitis in patients with sickle cell disease. Mycobacterium tuberculosis causes skeletal lesions in 1% of children with tuberculosis, typically manifested by lower thoracic vertebral osteomyelitis (Pott’s disease).

Pathogenesis

The pathogenesis of acute hematogenous osteomyelitis is dictated by the anatomy of growing bone in young children. The rich vascular supply of the metaphysis and its sluggish flow allow deposition of bacteria that enter via the nutrient artery (Figure 88-2). An absence of macrophages in the metaphyseal capillary loops allows bacterial replication, inducing an inflammatory response that may lead to abscess formation, infarction of bone, and necrosis. Acute hematogenous osteomyelitis is preceded by minor trauma to the site of infection in one-third of cases; resultant small hematomas may make the underlying metaphysis more favorable for bacterial deposition.

Figure 88-2 Pathogenesis of hematogenous osteomyelitis.

Transphyseal vessels in children younger than 18 months of age can lead to spread of the infection from the metaphysis into the epiphysis and joint space, causing a secondary septic arthritis. The growth plate, after it has formed, serves as a barrier to extension of infection into the epiphysis and joint. The hip or shoulder joint can be involved at any age because the metaphyses of the proximal humeri and femurs are located within their respective joints.

Clinical Presentation

Patients with acute hematogenous osteomyelitis describe localized bone pain that worsens over a brief period of time; the majority of these patients present to medical attention within 2 weeks of symptom onset. Pain precludes use of an affected extremity (pseudoparalysis). Fever is often present. Less common associated signs include malaise, anorexia, and vomiting. On physical examination of a patient with acute hematogenous osteomyelitis, swelling, erythema, warmth, and point tenderness that is out of proportion to the soft tissue findings may be present over the affected bone.

Ten percent of hematogenous osteomyelitis is categorized as subacute based on a slower progression of mild to moderate pain over the site of infection and the absence of systemic symptoms. Chronic osteomyelitis is characterized by waxing and waning pain and swelling that does not respond to prolonged antibiotics.

The clinical presentation of pelvic osteomyelitis includes pain in the hip, buttock, groin, lower back, or abdomen; gait abnormality; and, in some cases, fever. There is point tenderness over the affected bone and pain with manipulation of the hip. Distinguishing pelvic osteomyelitis and septic arthritis of the hip can be difficult, although range of motion of the hip joint is typically preserved in pelvic osteomyelitis.

Vertebral osteomyelitis can present with back, abdominal, chest, or leg pain; low grade–fever; and tenderness over the affected vertebrae. Fewer than 25% of patients demonstrate neurologic abnormalities. Symptoms can be subtle and slowly progressive, making diagnosis difficult. Vertebral osteomyelitis can be similar in presentation to diskitis but tends to affect older children and adolescents.

Chronic recurrent multifocal osteomyelitis is a distinct autoinflammatory disorder that is characterized by episodes of pain, swelling, and low-grade fever that recur over several years, radiographic findings of multiple lesions that have the appearance of osteomyelitis, an inability to isolate an infectious etiology, and a lack of clinical response to antimicrobial therapy. Girls are more commonly affected than boys, with symptom onset around 10 years of age.

Diagnosis

The diagnosis of osteomyelitis is made by a high index of clinical suspicion in the setting of confirmatory laboratory and imaging studies. Blood and bone cultures should be obtained before initiation of antibiotic therapy, if possible. If a joint is involved, synovial fluid cultures may aid in the microbiologic diagnosis. The peripheral white blood cell count and platelets may be normal or elevated. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are elevated in the majority of cases. The CRP typically peaks 48 hours after treatment initiation and returns to normal in 1 week. The ESR typically peaks 3 to 5 days after treatment initiation and may take 3 weeks to return to normal.

Plain radiographs show soft tissue swelling within 3 days of symptom onset; osteolytic lesions and periosteal elevation are apparent after 10 to 20 days; and after 1 month of symptoms, sclerosis of bone can be seen. Technetium-99 bone scanning has a sensitivity of 80% to 100% for osteomyelitis and can be helpful early on when plain films are normal and can identify multiple sites of infection, when present. Because the radionuclide bone scan can be falsely negative in 5% to 20% of children in the first few days of illness, magnetic resonance imaging (MRI) may be performed. MRI has a sensitivity of 92% to 100% for osteomyelitis and is effective in distinguishing soft tissue infection (e.g., cellulitis) from osteomyelitis. Pelvic and vertebral osteomyelitis are best imaged by MRI. Additionally, chronic osteomyelitis may have a different appearance from acute osteomyelitis on MRI (Figure 88-3).

Figure 88-3 Magnetic resonance imaging findings in early and late acute osteomyelitis.

The differential diagnosis of localized bone pain in children includes trauma, fracture, malignancy, and bone infarction. The differential diagnosis of multifocal bone lesions includes leukemia, neuroblastoma, and histiocytosis X.

Treatment and Prognosis

Treatment of osteomyelitis depends on the selection of appropriate antibiotic therapy and surgical intervention when indicated. Empiric parenteral antibiotics should be started while cultures are pending, the choice depending on the patient’s age and underlying medical condition, while ensuring coverage against S. aureus as well as adequate bone penetration. Antibiotic therapy is then modified based on culture results. Good outcomes are reported when conversion from parenteral to oral antibiotics is made in patients who are afebrile, demonstrating clinical improvement, and have a normalizing CRP. Intravenous (IV) therapy by means of a central venous catheter may be used to complete treatment at home for a patient in whom adherence to oral therapy is in question, but the risk of catheter complications increases with prolonged use. The total duration of therapy ranges from 4 to 6 weeks depending on the organism and clinical scenario.

Indications for surgery in a patient with osteomyelitis include (1) prolonged fever, pain, erythema, and swelling; (2) persistent bacteremia despite appropriate antibiotic therapy; (3) imaging results consistent with soft tissue or subperiosteal abscess; (4) the presence of necrotic bone; or (5) development of a sinus tract.

Complications of osteomyelitis include secondary septic arthritis and subsequent joint destruction, epiphyseal injury leading to impaired bone growth, development of chronic osteomyelitis, and pathologic fractures. The recurrence rate is approximately 2% to 5%. Poorer outcomes are seen with younger patients, a delayed diagnosis, and shorter durations of antibiotic therapy.

Etiology

Isolation of a bacterial organism from blood or synovial fluid of patients with septic arthritis occurs in 65% to 75% of cases. In general, the same pathogens cause septic arthritis as those that cause acute hematogenous osteomyelitis, including special clinical scenarios, such as hemoglobinopathies. In addition, pauciarticular arthritis of the large joints can be a complication of Borrelia burgdorferi infection in endemic areas.

Since the introduction of the conjugate Hib vaccine, infection with H. influenzae has become rare. Similarly, it is expected that a decrease in the cases of septic arthritis caused by the serotypes of S. pneumoniae contained within the heptavalent pneumococcal vaccine introduced in 2000 will be seen because an overall reduction in invasive pneumococcal disease has been shown.

Pathogenesis

Similar to acute osteomyelitis, hematogenous spread of bacteria to the vascular synovium is the most common cause of septic arthritis in children (Figure 88-4). The precise mechanism by which the presence of bacteria leads to joint destruction is unknown, but the resultant inflammatory response causes activation of host leukocytes, cytokine secretion, and chondrolysis. Degradation of the joint begins as early as 8 hours after infection and can lead to irreversible synovial fibrosis and bony ankylosis.

Figure 88-4 Septic arthritis.

Contiguous spread of bacteria into the joint space from rupture of a nearby focus of osteomyelitis occurs in approximately 10% of cases. Metaphyseal bone infection in children younger than 18 months of age can migrate through the growth plate to the epiphysis and then into the joint space by means of transphyseal blood vessels. The intracapsular location of the proximal metaphyses of the femur and humerus permits direct spread into the hip and shoulder joints, respectively.

Less frequently, septic arthritis develops as a consequence of direct penetrating injury or joint manipulation (such as intraarticular injections or prosthetic joint surgery).

Clinical Presentation

Septic arthritis is characterized by the acute onset of joint pain with systemic symptoms including fever and irritability. An older child may limp or refuse to walk, and an infant may demonstrate increasing irritability with passive movement of the joint. If the infection is in the upper extremity, the patient may refuse to use the affected joint.

On physical examination, there may be swelling, erythema, and warmth over the affected joint. Most helpful for diagnosis is the presence of severe limitation in movement of the affected joint and pain with manipulation, so-called micromotion tenderness. Infection of the hip may cause referred pain to the knee or thigh, and signs of external inflammation may be absent. Patients with septic arthritis of the hip classically keep the hip and knee flexed with the hip abducted and externally rotated, a position that alleviates the most pain.

Diagnosis

Rapid diagnosis of septic arthritis is crucial in preventing further joint destruction. Any child with fever, acute onset of pain, and limited range of motion on examination should be promptly evaluated. For microbiologic diagnosis, both blood and synovial fluid should be obtained for Gram stain and culture. Synovial fluid can be used to distinguish septic from other causes of arthritis: typically with a bacterial etiology, the fluid is cloudy, the WBC count is greater than 50,000/mm³, and polymorphonuclear cells predominate. Lyme arthritis can have a similar synovial fluid composition, so appropriate serologic testing is conducted as dictated by region. Measuring the levels of glucose and protein in the synovial fluid is generally not helpful. When N. gonorrhoeae is suspected in an adolescent patient, cultures of skin lesions and the throat, rectum, and cervix or urethra should also be sent.

Upon examination of the peripheral blood, the ESR is typically greater than 20 mm/h, and the CRP and peripheral WBC count are often elevated. CRP peaks by day 2 or 3 of treatment and normalizes in 7 to 9 days; ESR peaks by day 7 of treatment and normalizes in 3 to 4 weeks.

Plain radiographs in septic arthritis may be negative early on, but joint space widening and capsular distension can be seen (Figure 88-5); erosion of subchondral bone is evident 2 to 4 weeks into infection. Other pathologies such as fracture, osteomyelitis, and malignancy can be identified on the plain radiograph. With septic arthritis of the hip, plain films may again be negative, but the characteristic finding early on is swelling of the hip capsule and lateral displacement of the gluteal fat planes; later, there is upward and lateral displacement of the femoral head. Ultrasound of the hip can be performed to detect fluid in the joint and to guide arthrocentesis. Bone scan, CT scan, and MRI are typically not performed for diagnosis of septic arthritis, but can be useful for evaluating deep joints, such as the sacroiliac joint and identifying osteomyelitis.

Figure 88-5 Septic arthritis: imaging.

The differential diagnosis of septic arthritis includes transient (toxic) synovitis, viral arthritis, tuberculous arthritis, fungal arthritis, reactive arthritis, Reiter’s syndrome, juvenile idiopathic arthritis, rheumatic fever, trauma, malignancy, Legg-Calvé-Perthes disease, and a slipped capital femoral epiphysis (Table 88-1).

Table 88-1 Differential Diagnosis of Septic Arthritis

Reprinted with permission from Greene W: Netter’s Orthopaedics. Philadelphia, Saunders, Elsevier, 2006, p 157.

Treatment and Prognosis

Treatment of septic arthritis is aimed at joint decompression and sterilization for the prevention of serious sequelae. Arthrocentesis is performed both to obtain fluid for diagnosis and to decompress the joint. Repeated joint aspiration may be needed after reaccumulation of fluid. Prompt surgical drainage is warranted for septic arthritic of the hip or shoulder to prevent vascular compromise and ischemic necrosis of the femoral or humoral head, respectively.

Empiric IV antibiotic therapy should be started pending culture results even in patients with negative synovial fluid Gram stain results when the combination of clinical, laboratory, and imaging studies is suggestive of septic arthritis. Initial antibiotic choice depends on the patient’s age, clinical status, and local antibiotic resistance profiles.

The duration of antibiotic therapy is dictated by the pathogen involved, site of infection, and clinical response, as evidenced by symptoms and levels of inflammatory markers. Emerging data suggest that shorter courses (10 days) of oral antibiotics after brief IV administration may be equivalent in terms of clinical outcome to a more traditional longer course (30 days) of therapy.

Septic arthritis leads to residual joint problems in 10% to 25% of patients. These problems include abnormal bone growth, chronic joint dislocation, joint instability, and limited range of motion. Risk factors for complications include age younger than 6 months, delay of more than 4 days in diagnosis (and thus treatment), infection of adjacent bone, infection of the hip or shoulder, and infection with S. aureus or gram-negative organisms.