Septic arthritis occurs in all age groups, but especially in children <3 years of age. The reported incidence of septic arthritis varies from 2 to 5 per 100,000 per year in the general population to 28 to 38 per 100,000 per year in patients with rheumatoid arthritis. Although any joint can be infected and multiple joints can be involved, the hip and the knee account for nearly 80% of cases.
Bacteria are the usual pathogens in acute skeletal and joint infections. Bacteria may access the joint hematogenously, by direct extension from adjacent osteomyelitis, or from inoculation, as in arthrocentesis or femoral venipuncture. Hematogenous spread is the most common. Although Staphylococcus aureus is still the most common pathogen in osteoarticular infections, infection with community-acquired methicillin-resistant S. aureus and other multidrug-resistant organisms is increasing. In Europe, Kingella kingae (gram-negative coccobacilli) is reported to cause bone and joint infections, with only sporadic case reports of outbreaks in the United States.20 Widespread vaccination has decreased the prevalence of Haemophilus influenzae type B, reducing invasive disease. Common etiologic organisms also vary with the age of the child (Table 140-1).
TABLE 140-1Causes of Suppurative Arthritis in Children in Order of Decreasing Incidence ||Download (.pdf) TABLE 140-1 Causes of Suppurative Arthritis in Children in Order of Decreasing Incidence
|Newborn (0–2 mo) ||Infant (2–36 mo) ||Child (>36 mo) |
|Methicillin-sensitive Staphylococcus aureus (MSSA) ||MSSA ||MSSA |
|Methicillin-resistant S. aureus (MRSA) ||MRSA ||MRSA |
|Group B Streptococcus ||Streptococcus species ||Streptococcus species |
|Gram-negative bacilli ||Gram-negative bacilli ||Gram-negative bacilli |
|Neisseria gonorrhoeae ||Haemophilus influenzae ||N. gonorrhoeae |
|H. influenzae ||Unknown or unidentified || |
|Candida albicans* || || |
Even though septic infections of joints in children are uncommon, they are important because of their potential to cause permanent disability.
CLINICAL FEATURES AND DIAGNOSTIC IMAGING
The earliest signs and symptoms of septic arthritis are subtle. Neonates do not characteristically appear ill and, in half of cases, do not have fever. Older infants, toddlers, and children usually have fever and localizing signs. Infants may have only pseudoparalysis (absence of spontaneous movement) of an extremity or apparent pain on movement of the affected extremity. The child with hip or knee septic arthritis will limp or not walk at all. The child maintains the infected hip in flexion, abduction, or internal rotation. On physical examination of the septic knee, the manifestations are those of any localized infection (i.e., erythema, swelling, tenderness, and pain); these signs are not easily detected in the hip. Older children will appear ill, often with high fever (40.0 to 40.5°C [104 to 105°F]), with apprehension and irritability.
Children at special risk for septic infections of the bone and joint include those with underlying immune deficiency or systemic disease, including recent chickenpox, sickle cell anemia, rheumatoid arthritis, and inflammatory bowel disease. Maintain a high index of suspicion for septic arthritis in such children.
Plain film radiographs are nondiagnostic early in the course of infection but should be obtained to help identify osteomyelitis, fracture, or another process in the differential diagnosis.
Widening of the joint space with joint effusion and distention are late findings. Fat lines are displaced early in septic arthritis because of capsular distention. Views of the contralateral side may be useful for comparison. Ultrasonography is useful to document the presence of a joint effusion and aids in needle aspiration. CT and MRI provide improved soft tissue resolution and can aid in the diagnosis. The differential diagnosis is listed in Table 140-2.
TABLE 140-2Differential Considerations for the Acutely Inflamed Pediatric Joint ||Download (.pdf) TABLE 140-2 Differential Considerations for the Acutely Inflamed Pediatric Joint
Reactive or toxic synovitis
Acute rheumatic fever
Poststreptococcal reactive arthritis
Sickle cell crisis
Slipped capital femoral epiphysis
Juvenile rheumatic arthritis
If septic arthritis is suspected, obtain a CBC, blood cultures, erythrocyte sedimentation rate, C-reactive protein, and throat cultures; call orthopedics; and keep the child fasted/nothing by mouth. Arthrocentesis provides definitive diagnosis and should not be delayed while awaiting laboratory studies (see chapter 284, "Joints and Bursae"). Administer empiric antibiotics immediately if septic arthritis is suspected and orthopedic care is not available within 24 hours. Patients at risk for septic arthritis usually have temperature >38.5°C (101.3°F), a C-reactive protein >20 milligrams/L (usually high), leukocytosis (>12,000 cells/mm3), severe pain, tenderness on palpation, spasm, and refusal to walk.
Obtain joint fluid and send fluid for cell count, Gram stain, glucose, and culture and polymerase chain reaction testing.21 Isolation of an organism from the joint fluid does not occur in approximately one third of cases, but purulent fluid confirms the diagnosis when the clinical exam is suggestive. Fastidious or slow-growing organisms may not grow in culture. Likewise, the bacteriostatic effect of synovial fluid or prior empiric antibiotic therapy may decrease the sensitivity of joint aspirate cultures. When blood cultures are obtained, they are positive in less than half of cases, but they are the only source from which the causative agent is isolated in about 10%. Polymerase chain reaction studies of joint fluid improve organism detection.21,22
Concurrent infections at other sites may be associated with septic arthritis, and culture of those sites may help define the pathogen (e.g., urine gram-negative bacilli; skin/wound S. aureus; urethra, cervix, rectum, and pharynx Neisseria gonorrhea).
Treatment is prompt joint drainage and wash-out (open, in the operating room) followed immediately by IV antibiotic administration. If orthopedic care will be delayed, then IV antibiotics should be started. Table 140-3 lists possible choices for initial antibiotic therapy, including empiric treatment. The prognosis depends on the length of time between symptom onset and treatment. A treatment delay of more than 4 days increases the likelihood of orthopedic complications, and infants have less favorable outcomes.
TABLE 140-3Initial Antibiotic Therapy of Acute Suppurative Arthritis in Children ||Download (.pdf) TABLE 140-3 Initial Antibiotic Therapy of Acute Suppurative Arthritis in Children
JUVENILE IDIOPATHIC ARTHRITIS
Juvenile idiopathic arthritis is an umbrella term that has replaced the term juvenile rheumatoid arthritis. Juvenile idiopathic arthritis includes a heterogeneous group of arthritides of unknown cause that develop in children <16 years old. A detailed presentation of each type of arthritis is beyond the scope of this chapter. Systemic juvenile idiopathic arthritis is discussed in the following paragraphs.
Systemic juvenile idiopathic arthritis is associated with high fevers and chills, characteristically with spikes to at least 39°C (102.2°F) for a minimum of 2 weeks. There is also an accompanying characteristic faint erythematous macular coalescing rash that can involve the trunk, palms, and soles. The arthritis is usually polyarticular. Associated findings are hepatosplenomegaly, lymphadenopathy, and pleuritis or pericardial effusion. Laboratory evaluation is not highly specific but can be significant for anemia, leukocytosis, thrombocytosis, elevated acute phase reactants (erythrocyte sedimentation rate and C-reactive protein), and elevated serum immunoglobulins. Arthrocentesis may be necessary to exclude acute septic arthritis, especially in oligoarticular disease. Early in the course, radiographs demonstrate only soft tissue swelling and, possibly, synovial effusions. Bone and cartilage destruction occurs later.
One of the most life-threatening complications is an entity called macrophage activating syndrome caused by macrophage and T-lymphocyte proliferation and is characterized by multi-organ system failure. Clinical findings can include high fever, purpura, spontaneous mucosal bleeding, altered mental status, and hepatosplenomegaly. Laboratory evaluation can reveal pancytopenia, liver dysfunction, disseminated intravascular coagulopathy, hyperferritinemia, hypertriglyceridemia, and low fibrinogen. Treatment may include symptomatic care in addition to pulse corticosteroids and cyclosporine A or a biologic.23
Hospital admission is needed to establish the diagnosis and to treat suspected acute suppurative arthritis while synovial fluid cultures are pending.
The initial therapy for patients with an established diagnosis includes a short-term trial of nonsteroidal anti-inflammatory drugs, following which, if disease activity is still present, methotrexate is usually started. Corticosteroids are used less commonly than in the past, but can still be useful in overwhelming systemic illness, including pericarditis, myocarditis, or iridocyclitis unresponsive to other therapy. A pediatric rheumatologist should direct management strategies, including intra-articular glucocorticoid injections and use of methotrexate (current first-line agent) and other biologic or nonbiologic disease-modifying antirheumatic drugs.24
Legg-Calvé-Perthes disease is a hip disorder that generally has an onset between the ages of 4 and 9 years old in 80% of patients, with a range of occurrence from 2 to 13 years. It is the best known form of avascular necrosis or osteochondrosis, occurs in the femoral head, and should be considered in the differential diagnosis of the limping child in this age range. Males outnumber females by a ratio of 4:1, and it is bilateral in 10% of cases. Most children with the disorder are small for their age, with delayed skeletal maturation. Any primary or secondary ossification center can undergo changes as described below with necrosis and alteration of bone growth, with more common sites being the navicular (Koehler's disease), second metatarsal (Freiberg's disease), capitellum (Panner's disease), and lunate (Kienbock's disease), as well as the apophyses of the patella (Sinding-Larsen-Johanssen disease), tibia (Osgood-Schlatter disease), and calcaneus (Sever's disease).25
Legg-Calvé-Perthes disease begins with repeated episodes of ischemia of the femoral head, leading to infarction and necrosis. Avascular necrosis is then complicated by a subchondral stress fracture. Reossification and remodeling (resorption) occur over 2 to 4 years. The femoral head flattens and collapses and is prone to subluxation. The outcome ranges from complete recovery of the joint to a painful hip joint with a restricted range of motion, muscle spasms, and soft tissue contractures, and depends largely on the age of onset and the potential of the femoral head to remodel.
The onset of disease is usually insidious. Mild hip pain and limp have been present for weeks to months before making the diagnosis. Initially, pain is mild to none and is often referred to the anteromedial thigh or knee. Physical findings include decreased hip abduction and internal rotation. Sometimes the initial presentation is associated with trauma. Proximal thigh atrophy, and in advanced cases, limb shortening may also be noted.
Radiographically, in the initial stage of the disease (1 to 3 months), the capital femoral epiphysis fails to grow because of the lack of blood supply. The hip radiograph demonstrates widening of the cartilage space of the affected hip and a small-size ossific nucleus of the femoral head (Figure 140-31). Next, a subchondral stress fracture line in the femoral head is evident (Caffey's sign). As the disease progresses, new bone is deposited on avascular trabeculae. Subsequently, calcification of the more radiopaque necrotic marrow occurs, with resultant crushing of the avascular trabeculae in the dome of the epiphysis. Further distortion of the femoral head progresses (although this is not inevitable), along with subluxation and extrusion of the femoral head from the acetabulum.
Legg-Calvé-Perthes disease: note the flattened and radiopaque left femoral epiphysis.
Diagnosis of Legg-Calvé-Perthes disease demands a high index of suspicion, because initial radiographs sometimes are normal. Bone scan and MRI can detect disease before plain film abnormalities are evident. The differential diagnosis includes toxic synovitis, slipped capital femoral epiphysis, acute rheumatic fever, tuberculosis arthritis, tumors such as eosinophilic granuloma, osteoid osteoma, osteoblastoma, and lymphoma. Initial management is non–weight bearing and referral to a pediatric orthopedist for definitive care.
Osgood-Schlatter disease is an apophysitis of the tibial tubercle resulting from repeated normal stresses or overuse. These repetitive stresses imposed by the patellar tendon on its site of insertion result in a series of microavulsions of the ossification center and the underlying cartilage. Inflammation causes patellar tendonitis and the development of a remarkable prominence, induration, and tenderness of the tibial tuberosity. There is no avascular necrosis of the tibial tubercle. Children are usually between 10 and 15 years of age at time of onset; it more commonly occurs in running or jumping athletes. Boys are affected more often than girls, and most cases are bilateral, although symptoms are commonly asymmetric.
Signs and symptoms of Osgood-Schlatter disease are chronic, intermittent pain and tenderness over the anterior aspect of the knee and the tibial tuberosity. Pain is aggravated by activities such as running, kneeling, squatting, and climbing stairs; pain improves with rest. On examination, there is a prominence and soft tissue swelling over the tibial tubercle. The patellar tendon is tender and thick. The remainder of the knee examination usually is normal, and there is no knee effusion.
Radiographs are not essential, but are usually obtained. Radiographic findings of soft tissue swelling and irregularities of the tibial tubercle are nonspecific (Figure 140-32). The irregularity of the ossification of the tibial tubercle is normal in this age group. A lateral knee radiograph may show prominence of the tibial tuberosity, calcification in the tibial tubercle region, or separate ossicles from the anterior border of the tubercle.
Lateral radiograph illustrating Osgood-Schlatter disease with prominence of the tibial tuberosity in addition to ossicles separate from the anterior border of the tubercle (arrow). [Photo used with permission of Wake Medical Center, Raleigh, NC.]
The disease is self-limited, and most patients' symptoms respond to rest and temporary avoidance of the offending activity. However, complete avoidance of activity or sports is not essential. Immobilization is actually contraindicated and can lead to rapid atrophy of the quadriceps muscle. Physical therapy and flexibility exercises to stretch and strengthen the quadriceps and hamstring muscles may help to alleviate stress on the tubercle and avoid recurrences. Applying ice after activity may decrease swelling, and pain can be controlled with nonsteroidal anti-inflammatory drugs. Corticosteroids should not be injected into the patellar tendon or para-apophyseal soft tissues. Parents should be provided reassurance that the condition is benign and self-limited and will resolve after closure of the proximal tibial growth plate. Rarely, an ossicle may persist after skeletal maturity that causes pain and may require excision.
Acute rheumatic fever primarily affects children of school age. The incidence of acute rheumatic fever has steadily fallen in developed countries over the past 50 years. However, sporadic cases of invasive group A β-hemolytic streptococcal infections with presumably more virulent strains means that outbreaks of acute rheumatic fever continue to be regularly reported in North America. It is preceded by infection with certain strains of group A β-hemolytic Streptococcus (mucoid types 3, 5, and 18). The connective tissue of the heart, joints, CNS, and subcutaneous tissues and skin are targeted by host antibodies that develop secondary to streptococcal infection. The carditis is an endomyocarditis, with valvulitis primarily involving the mitral and aortic valves. The arthritis is characterized by synovial edema and periarticular swelling with joint effusions.
The child develops the disorder 2 to 6 weeks following streptococcal pharyngitis. Although nonspecific symptoms of systemic illness predominate early on, physical examination eventually reveals evidence of arthritis, carditis, choreiform movements, erythema marginatum, or subcutaneous nodules, individually or in combination. Table 140-4 lists the Jones criteria for establishing a diagnosis of acute rheumatic fever. Either two major criteria or one major and two minor criteria plus evidence of an antecedent streptococcal infection are necessary to establish the diagnosis.
TABLE 140-4Revised Jones Criteria for the Diagnosis of Acute Rheumatic Fever ||Download (.pdf) TABLE 140-4 Revised Jones Criteria for the Diagnosis of Acute Rheumatic Fever
|Major Criteria ||Minor Criteria |
|Carditis ||Fever |
|New or changing murmurs ||Arthralgia |
|Cardiomegaly, congestive heart failure ||History of previous attack of acute rheumatic fever |
|Pericarditis ||Elevated erythrocyte sedimentation rate, C-reactive protein |
|Migratory polyarthritis || |
|Chorea ||Prolonged PR interval on ECG |
|Erythema marginatum ||Rising titer of antistreptococcal antibodies |
|Subcutaneous nodules || |
Arthritis occurs in 60% to 75% of initial attacks and is characterized as a migratory, fleeting polyarticular arthritis primarily affecting the large joints. Carditis occurs in one third of new cases and may be mild or severe. Its presence is heralded by any combination of a new cardiac murmur, tachycardia, a gallop rhythm, a pericardial friction rub, congestive heart failure, or a hyperactive precordium. Sydenham chorea occurs in 10% of cases and may have its initial appearance months following a streptococcal infection. Chorea may be the sole manifestation of acute rheumatic fever. The skin rash of acute rheumatic fever (erythema marginatum) is described as serpiginous and persists only for several days. It usually coexists with the presence of carditis in some form. Subcutaneous nodules are rarer and are located on the extensor surfaces of the wrists, elbows, and knees. The greatest morbidity and mortality are due to carditis.
Diagnostic studies are used to clarify the associated antecedent infection by group A Streptococcus (a pharyngeal swab for culture, antistreptolysin titers, or streptozyme titers) or are used to identify and assess the presence and extent of carditis. Obtain an ECG to identify conduction delays or hypertrophy. A chest x-ray serves to identify cardiac dilatation or pulmonary vascular congestion or edema. Echocardiography identifies valvulitis or valvular insufficiency (see chapter 126, "Congenital and Acquired Pediatric Heart Disease").
The differential diagnosis includes juvenile idiopathic arthritis, septic arthritis, Kawasaki's disease, viral or other forms of cardiomyopathy, leukemias, and other forms of vasculitis, including Henoch-Schönlein purpura, and drug reactions. Rarely, tumors of the CNS require differentiation from acute rheumatic fever when the child's sole clinical manifestation is chorea.
ED treatment is directed primarily toward the management of complicating features of carditis. In the absence of cardiac or hemodynamic instability (and such is the rule), early consultation with a pediatric cardiologist is recommended, and admission to the hospital is generally advised in the early stages until the diagnosis is confirmed. Arthritis is managed with high-dose aspirin therapy (75 to 100 milligrams/kg/d) to achieve a serum salicylate level of 20 to 30 milligrams/dL. Reduce the aspirin dose after approximately 1 week to 50 milligrams/kg/d for an additional 4 to 6 weeks. Weigh the benefits and risks of aspirin therapy during influenza season (i.e., association with Reye's syndrome) carefully. Carditis or congestive heart failure is treated with prednisone, 1 to 2 milligrams/kg/d. Continue prednisone for 2 weeks after the resolution of symptoms and the return of the erythrocyte sedimentation rate to normal, and then taper steroids over 4 to 6 weeks. Chorea can be treated with haloperidol, 0.01 to 0.03 milligram/kg/d in four divided doses. All children with acute rheumatic fever are treated with penicillin, even if the cultures for group A Streptococcus are negative. The dose of benzathine penicillin is 600,000 units IM if <27 kg, and 1.2 million units IM if >27 kg. Benzathine penicillin G can be administered in a single dose of 1.2 million units. Penicillin V administered PO is also effective. Erythromycin is substituted for the penicillin-allergic patient. Therapy is administered for 10 days.
Administration of prophylactic antibiotics for 5 years is recommended for children without cardiac involvement; patients with carditis need lifelong prophylaxis. Prophylactic regimens include benzathine penicillin G, 1.2 million units administered IM every month, or daily oral penicillin V potassium or sulfadiazine.
POSTSTREPTOCOCCAL REACTIVE ARTHRITIS
Poststreptococcal reactive arthritis is a poorly understood clinical syndrome in which arthritis of one or more joints occurs after group A streptococcal infection of the pharynx. It is not certain whether poststreptococcal reactive arthritis represents a mild or early form of acute rheumatic fever or whether it is an entirely separate entity. It falls into a group of postinfectious reactive arthritides with multiple etiologies.26
Poststreptococcal reactive arthritis is not associated with carditis or other major Jones criteria and is a milder illness. Poststreptococcal reactive arthritis also begins sooner (approximately 10 days) after streptococcal infection than does acute rheumatic fever (approximately 21 days). The arthritis in poststreptococcal reactive arthritis is generally more severe and prolonged and unusually resistant to treatment with salicylates, in contrast to the migratory salicylate-sensitive arthritis generally associated with acute rheumatic fever.
The differentiation between acute rheumatic fever and poststreptococcal reactive arthritis is clinical. The arthritis of acute rheumatic fever is classically a migratory polyarthritis, whereas the arthritis of poststreptococcal reactive arthritis is a nonmigratory mono- or oligoarthritis. Acute rheumatic fever poststreptococcal nonsuppurative sequelae are more commonly observed in younger patients (mean age, 12 ± 4 years). The typical patient with reactive arthritis is older, but it may occur in children as young as 4 years of age. Erythema nodosum and erythema multiforme are frequently associated with poststreptococcal reactive arthritis, whereas they are encountered only infrequently in cases of acute rheumatic fever.
To establish the diagnosis of poststreptococcal reactive arthritis, establish antecedent infection with group A Streptococcus. If group A Streptococcus is recovered from the throat, treat with antibiotics. The diagnosis of poststreptococcal reactive arthritis should be made only after careful historical and clinical evaluation for nonsuppurative complications or other causes of polyarthritis. Antibiotic prophylaxis may be considered on a short-term basis. If, after further evaluation, there is no evidence of carditis or chorea, prophylaxis may be discontinued. Treatment of poststreptococcal reactive arthritis is nonsteroidal anti-inflammatory drug analgesia.
TRANSIENT SYNOVITIS OF THE HIP
Toxic or transient synovitis is a benign, self-limiting inflammatory process of the hip. It afflicts males more than females and is the most common cause of acute hip pain in children <10 years of age. The peak incidence is between ages 3 and 6 years old, but it is reported from 9 months of age to adolescence. It is eight times more frequent than septic arthritis of any joint. The cause is unknown, but it is most often believed to be a postviral illness sequela, but trauma, bacterial infection, and postvaccine or drug-mediated reactions have also been cited as possible causes. Arthralgia and arthritis are secondary to a transient inflammation and hypertrophy of the synovial membrane.
Symptoms are characterized by an abrupt onset of unilateral hip pain, limp, and restricted hip motion (preferentially held in abduction and external rotation). The child may complain of pain in the anteromedial or anterolateral thigh and knee. Although children complain of discomfort with movement of the limb, it generally remains possible to put the hip through a full range of motion. This is in contrast to the septic hip in which pain and spasms are more severe and range of motion is decreased. The child is nontoxic appearing, and other signs of systemic illness are absent. There can be either no fever or a low-grade temperature elevation. The mean WBC count and erythrocyte sedimentation rate are significantly lower than in septic arthritis, but they cannot be used to distinguish between transient synovitis and septic arthritis in individual patients (see discussion of acute septic arthritis above).
Radiographs of the hip may be normal or may demonstrate an effusion. There are no bone changes associated with transient synovitis. US is more sensitive than plain films at detecting joint effusions, although accuracy is decreased in patients <1 year of age. Reports of an effusion of the hip by US in toxic synovitis vary from 50% to 95%.
The differential diagnosis includes Legg-Calvé-Perthes disease and septic arthritis of the hip. Less common causes include acute rheumatic fever, juvenile idiopathic arthritis, and, rarely, tuberculosis of the hip.
If the peripheral WBC count and erythrocyte sedimentation rate are substantially elevated and a hip effusion is noted on radiograph or US, perform a diagnostic arthrocentesis and obtain orthopedic consultation to exclude a septic joint. Send synovial fluid for Gram stain, aerobic and anaerobic cultures, and acid-fast bacilli with culture. Synovial fluid is sterile and clearly transudative with no organisms on Gram stain.
Treatment is with rest until the pain resolves, usually 3 to 7 days, followed by limited activity for 1 to 2 weeks. Nonsteroidal anti-inflammatory drugs are the first-line therapy for pain. There are no sequelae from transient synovitis. As long as the diagnosis is certain, reevaluation by the primary care physician can be arranged within 2 weeks.