Pediatric Septic Arthritis

The most common route by which microorganisms enter a joint is by hematogenous spread to the synovium. Less commonly, entry occurs directly following a penetrating trauma or contiguously from an adjacent osteomyelitis. Because of their unique anatomy, neonates and young children often have coexisting septic arthritis and osteomyelitis. The bony cortex is thin, and the periosteum is loose. Blood vessels that connect the metaphysis and epiphysis serve as a conduit by which bony infection may easily reach the joint space.

Proteolytic enzymes released by inflammatory cells can damage joint cartilage. In addition, inflammatory mediators, bacteria, and pus increase pressure within the joint, compress intra-articular vessels, and impair blood supply to the cartilage and adjacent bone. Pressure necrosis within any joint may destroy synovium or cartilage, but septic arthritis of the hip is a true orthopedic emergency. In the hip, if the condition remains undiagnosed and untreated, contiguous spread may cause ligamentous damage, avascular necrosis of the femoral head, dislocation, and osteomyelitis.

Infectious agents

In neonates (aged < 2 mo), Staphylococcus aureus is the most common cause of septic arthritis (SA), but Escherichia coli, group B streptococci, and other gram-negative bacilli also cause the disease.

In children aged 2 months to 5 years, Haemophilus influenzae type B was the most common cause of SA prior to the widespread use of vaccines; S aureus is now the most common cause. In a series of 61 children diagnosed with a known pathogen from 1975-1985, H influenzae type B caused the infection in about half of the children.[1] In contrast, among 46 children diagnosed with septic arthritis from 2000-2006, S aureus was the cause in 31 (67%).[2] Other etiologies include group A streptococci and Streptococcus pneumoniae. Community-acquired methicillin-resistant S aureus (MRSA-CA) is an increasingly common cause of SA in children.

In adolescents, Neisseria gonorrhoeae is the suspected cause for patients with either polyarticular or monoarticular disease. Group A streptococcus is reported in numerous children with active varicella-zoster infection. Salmonella is suspected in individuals with sickle cell anemia. Salmonella typhi has also been reported as a cause of septic hip arthritis in immunocompetent infants and children.[3]

Mycobacterium tuberculosis is a rare cause of chronic pyogenic arthritis. If identifiable risk factors are present, then a purified protein derivative (PPD) should be placed for the child with culture-negative disease. Kingella kingae has been noted to cause SA in children younger than 5 years in Israel and is an emerging pathogen in the United States. Rarely, fungi or anaerobes may be found within a septic joint.

A common cause of reactive arthritis is the spirochete Borrelia burgdorferi. Children typically present with a monoarthritis, in the absence of fever, weeks to months after being bitten by a tick. Less common causes of reactive arthritis include mycoplasma and viruses.

Occurrence in the United States

Septic arthritis (SA) is more common in children than adults, but the actual incidence is unknown. From 1979-1996, a tertiary-care children's hospital reported just 82 children with either confirmed or suspected SA of the hip.[4] From 2000-20004, 34 such cases were diagnosed at a separate tertiary-care children's hospital.[5] Data from older studies are somewhat obsolete, because effective vaccines have virtually eliminated the most common etiologic agent, Haemophilus influenzae type B.

With the dramatic increase in MRSA-CA, the clinical impression of pediatricians and pediatric emergency medicine physicians is that a corresponding increase in the incidence of SA has been observed.[6] However, large, population-based studies to prove this trend are lacking. In fact, a study by Okubo et al reviewed the US hospital discharge records of pediatric septic arthritis patients for 2006, 2009 and 2012 and reported a decreasing trend in incidence (4.23, 3.64, and 3.28 per 100,000 children in 2006, 2009, and 2012, respectively). The study also reported a higher hospitalization rate in children who were male and between 0-4 years of age and living in lower-income areas. The most frequently affected sites of infection were in the large joints at the lower limbs and these infections and the age category of 10-14 years of age were associated with osteomyelitis and bacteremia/septicemia comorbidities.[7]

Subgroups of children who are at high risk for SA include neonates, individuals with hemophilia who are subject to hemarthrosis, and individuals who are immunocompromised, such as those with sickle cell anemia or human immunodeficiency virus (HIV) infection or those treated with chemotherapy.

A study by Okubo et al reviewed the US hospital discharge records of pediatric septic arthritis patients for 2006, 2009 and 2012 and reported a decreasing trend in incidence (4.23, 3.64, and 3.28 per 100,000 children in 2006, 2009, and 2012, respectively). The study also reported a higher hospitalization rate in children who were male and between 0-4 years of age and living in lower-income areas. The most frequently affected sites of infection were in the large joints at the lower limbs and these infections and the age category of 10-14 years of age were associated with osteomyelitis and bacteremia/septicemia comorbidities.[7]

A study by Patankar et al found no clear seasonal variation in the incidence of septic arthritis in children in the United States, except in northeastern states. In the Northeast, a higher percentage of cases occurred in the fall and summer (28%) than in the winter (21%).[8]

Sex- and age-related demographics

A higher incidence of SA is reported among boys than girls; some series report that boys are affected twice as frequently as are girls. However, a series of 82 children with SA of the hip found no sex predilection.[4]

SA occurs among all age groups but is most common in younger children, peaking in those younger than age 3 years.

Time to diagnosis is the most important prognostic factor in septic arthritis (SA). Early institution of therapy helps to prevent degenerative arthritis. Diagnosis may be delayed in young infants, which leads to a poorer outcome.

Other poor prognostic factors include infection of the hip joint, which may lead to aseptic necrosis of the femoral head; infection with S aureus; and a prolonged passage of time before the synovial fluid is sterilized.

Meningitis (10-30%), osteomyelitis (5-10%), cellulitis (10-30%), and pneumonia (5%) are potential complications in young children with septic arthritis resulting from hematogenous spread of H influenzae type B. Osteonecrosis, growth arrest, and sepsis are potential complications from SA of any etiology.

Because of the availability of antibiotics, children rarely die from septic arthritis or its complications. Although chronic arthritis is uncommon, the short-term morbidity and costs, in terms of prolonged antibiotic therapy and hospitalizations, may be substantial.

Joint pain or swelling

Acute joint inflammation marked by severe pain and swelling is the hallmark of septic arthritis (SA). Joint pain results from stretching of the fibrous joint capsule. If lower extremity joints are involved, parents often report that children cannot bear weight and that they resist all efforts to move the involved joint.

Children typically have involvement of a single joint; lower extremity joints, especially the knee and hip, account for most cases. The elbow is the most common upper extremity joint to become infected. Neonates are more likely to have infection in multiple joints (polyarticular disease).

Pseudoparalysis

A septic joint may be so painful that a child may not tolerate any range of motion, resulting in pseudoparalysis. However, ability to actively or passively move the joint does not exclude SA.

If supported by a physical examination of the joint, this history helps to distinguish SA from less painful causes of arthralgia, such as transient synovitis of the hip, postinfectious or reactive arthritis, or traumatic hemarthrosis.

Septic arthritis versus transient synovitis

One retrospective series determined that a history of fever and difficulty of bearing weight on a limb, along with an erythrocyte sedimentation rate greater than 40 mm/h and a peripheral white blood cell (WBC) count of more than 12,000 cells/μL, were independent variables that best distinguished SA from transient synovitis.[4] The probability of SA was 99.6% for children with all 4 factors and 93.1% for those with any 3 factors. In another series, none of the children with transient synovitis had fever, and fever was found to be the most influential predictor in distinguishing between the 2 conditions.[5]

Decreased or absent range of motion, joint tenderness, swelling, warmth, and erythema are common physical signs of septic arthritis (SA). However, because of the deep location of the hip joint, there may be no erythema or swelling noted. Children orient an affected joint in such a way as to minimize the pain. The hip is flexed, abducted, and externally rotated. The knee, ankle, and elbow are partially flexed, whereas the shoulder is adducted and internally rotated. (See the image below.)

Emergency room photograph of an infant with septic arthritis of the left hip. The child holds his hip rigidly in the classic position of flexion, abduction, and external rotation, a position that maximizes capsular volume. The patient is relatively comfortable as long as the hip joint remains immobile in this position.

In one study, among 82 children with septic arthritis of the hip, 78 (95%) were unable to bear weight on the affected limb at presentation.[4]

Diagnosis is suspected in children who present with monoarthritis of a lower extremity. In a series of 95 children with septic arthritis (1975-1985), over 90% had involvement of a single joint of a lower extremity.[1] One notable exception is gonococcal septic arthritis. This results from the hematogenous spread of the organism, with fever, chills, rash, tenosynovitis, and migratory polyarthritis, which often leads to monoarticular infection.

Burgess reported a case series of 9 children with septic arthritis of the temporomandibular joint[9] . Physical findings in these children included pre-auricular swelling and trismus and 7/9 had mastoiditis. The study also found that associated thrombophlebitis of the lateral sinus or intracranial collections occurred in 7 patients.

Fever

In a series of 95 children with SA, most had a low-grade fever, but one third were afebrile at presentation.[1] In another study, 83% of children with SA had a recent fever, but only half were febrile at emergency department presentation.[2] Absence of fever should not sway the clinician from the diagnosis.

On the other hand, the presence or absence of fever may be helpful in distinguishing SA from transient synovitis of the hip. Each condition presents as an acutely irritable hip in a young child and may be associated with an effusion. In general, children with transient synovitis are afebrile, while those with SA have more diminished range of motion.

Diagnosis of septic arthritis (SA) is established by a combination of clinical findings and results of synovial fluid analysis. Clinicians should have a low threshold for performing arthrocentesis, especially for children with a painful monoarthritis, significantly limited range of motion, and no plausible noninfectious explanation.

Emergency department physicians are usually adept at performing arthrocentesis of most joints. The knee joint, for example, can usually be entered fairly easily using either a medial or superolateral approach. However, aspiration of fluid from the hip typically requires the involvement of a radiologist and an orthopedic surgeon.

General practices that help to ensure the safety and success of arthrocentesis include liberal use of sedatives and analgesics, joint immobilization, sterile technique, and local anesthesia. Use of a needle large enough (18-20 gauge) to aspirate what may be viscous synovial fluid is also necessary.

When septic arthritis (SA) is suspected, synovial fluid should be obtained for a complete blood count (CBC), glucose, Gram stain, and culture. Synovial culture has poor sensitivity (60-70%), and the data that establish the typical characteristics of synovial fluid in septic arthritis were collected in the era of widespread H influenzae type B infection. How these characteristics will change in the current era remains to be seen. Similarly, although blood cultures should be obtained, they have relatively low yields.

A synovial fluid WBC count of more than 50,000/mL suggests SA, especially if the count exceeds 100,000/mL or if a predominance of polymorphonuclear cells is observed. Still, counts are often lower, and high counts may be associated with other conditions.

A retrospective study by Dart et al that included 238 patients with septic arthritis, Lyme arthritis, and other arthritis reported that synovial fluid WBC count is not helpful in differentiating septic from Lyme arthritis and that rapid Lyme diagnostics would be useful.[16]  [17, 18]  A separate report found no differences in the synovial fluid white blood cell or neutrophil counts among children with Lyme or septic arthritis of the knee.[19]

The synovial fluid glucose concentration averages 30% of that in the serum, a finding unique to SA. The erythrocyte sedimentation rate is typically elevated, but in one series, fewer than one half of children with septic arthritis had peripheral WBC counts above 15,000 cells/μL.

Although often elevated, a peripheral WBC count within the reference range does not rule out septic arthritis. C-reactive protein (CRP) is a more sensitive marker for septic arthritis than is the peripheral WBC count. The CRP level is also a more sensitive diagnostic marker and a better indicator of response to treatment than the erythrocyte sedimentation rate.[20] In one study, a CRP level of more than 2 mg/dL was found to be a strong independent risk factor for SA of the hip among children presenting with hip pain.[5]

A study evaluated the clinical utility of polymerase chain reaction (PCR) as a supplemental diagnostic tool in the evaluation and the treatment of children with septic arthritis. The study concluded that PCR provides supplemental information for diagnostic confirmation through an increased rate of detection of bacteria.[21]

Radiography

Although plain radiography may reveal an effusion as widening of the joint space with displacement of fat planes, it is insensitive in the diagnosis of septic arthritis (SA). Radiography may be most helpful in screening for etiologies other than SA as a cause of joint pain. For example, it may reveal bony changes suggestive of osteomyelitis, bony tumors or fractures as the source of swelling, and Legg-Perthes disease or a slipped capital femoral epiphysis, which are diagnostic considerations in a child with an irritable hip.

Ultrasonography

Ultrasonography is a simple and relatively inexpensive technique for detecting a hip effusion. This test has a greater sensitivity than plain radiography and is becoming the modality of choice to reveal hip effusions. Ultrasonography is also used to guide the aspiration needle if an effusion is detected.

In a study of 96 children suspected of having septic arthritis of the hip, 40 had normal ultrasonographic findings and no septic arthritis.

Ultrasonography has several advantages over computed tomography (CT) scanning in this setting, including eliminating radiation exposure and guiding the aspiration of deep joints, such as the hip.

Scintigraphy

Scintigraphy has a limited role in most cases of SA, but it may be helpful if multifocal disease is suspected in neonates. It also assists with the detection of an associated osteomyelitis.

Hospitalize all children presumed to have septic arthritis (SA) for empiric intravenous antibiotic therapy. After 2-3 days of immobilization, encourage early passive range of motion.

The optimal duration of antibiotic therapy is not defined, and recommendations vary from 1-6 weeks. Thus, institutional practices will prevail. In general, 3-4 weeks of antibiotic therapy is used to treat S aureus,H influenzae type B, or S pneumoniae infections, whereas gonococcal infections are treated for 7-10 days.

Consultations

Consultation may be indicated with an orthopedic surgeon. Septic arthritis of the hip requires emergent irrigation and drainage to minimize risk of aseptic necrosis of the femoral head. Consultation with an infectious diseases specialist is particularly indicated if the diagnosis is uncertain or if the microbiology is unusual.

Splint the affected joint in a functional position for the first few days after a diagnosis of septic arthritis (SA). Encourage early passive range of motion to stretch tendons and prevent contractures.

Once an organism is identified, an appropriate antibiotic is selected, and the child is demonstrating a good clinical response, continue outpatient therapy with either high-dose oral antibiotics or parenteral antibiotics. Antibiotics readily enter the joint fluid in high concentrations after oral administration. Frequent revisits to the physician to ensure compliance and good clinical response are essential.

No studies have compared outcomes for children with SA undergoing arthrotomy versus aspiration alone. Traditionally, for uncomplicated septic arthritis involving joints other than the hip or shoulder, serial needle aspirations are performed. These may be discontinued once fluid no longer reaccumulates. Failure to reach this goal is an indication for arthrotomy and open drainage.

Urgent arthrotomy and open drainage is usually performed in septic arthritis of the hip or shoulder, septic arthritis of other joints if no improvement occurs within 3 days of starting antimicrobial therapy, or if a large amount of pus or debris is aspirated during diagnostic arthrocentesis. However, in one study of 62 children with septic arthritis of the hip, 50 were treated successfully with aspiration and antibiotics alone.[22]

Typically, a clinician chooses an antibiotic before synovial fluid culture results are known. Thus, the child's age and risk factors, as well as Gram stain results, should influence initial antibiotic coverage. Neonates are at risk for infection with gram-positive organisms, such as S aureus or group B streptococci, and gram-negative organisms, such as E coli.

For neonates without meningitis, a semisynthetic penicillin (eg, oxacillin) plus an aminoglycoside (eg, gentamicin) may be used. Neonates with concomitant meningitis and septic arthritis (SA) present a therapeutic challenge. Oxacillin does not penetrate the blood-brain barrier well, and ampicillin, although it offers better cerebrospinal fluid levels, does not provide adequate coverage against S aureus. In this case, a combination of vancomycin and a third-generation cephalosporin, such as ceftriaxone, is a reasonable choice for initial coverage.

S aureus is the most common cause of SA among nonneonates. Oxacillin alone should provide adequate coverage in older children who are immunocompetent, assuming that they are immunized for H influenzae type B. However, in communities in which MRSA-CA is prevalent, clindamycin is a better initial choice. A third-generation cephalosporin is the initial therapy for an adolescent possibly infected with gonococcus.

Once culture results and sensitivities are known, antibiotic selection can be more specific. For example, a child with group A beta hemolytic streptococcus (GABHS) infection could be treated with penicillin, whereas one growing anaerobes requires clindamycin.

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Oxacillin (Bactocill in dextrose)

Oxacillin is a semisynthetic penicillin that is effective against staphylococci.

Gentamicin

Gentamicin is an aminoglycoside with good gram-negative activity. Dosing regimens are numerous; adjust the dose based on CrCl and changes in the volume of distribution.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Ceftriaxone arrests bacterial growth by binding to 1 or more penicillin-binding proteins.

Penicillin G potassium (Pfizerpen)

This agent is active against most gram-positive organisms except S aureus, as well as some anaerobes. It interferes with the synthesis of cell wall mucopeptide during active multiplication, resulting in bactericidal activity against susceptible microorganisms.

Clindamycin (Cleocin)

Clindamycin is active against most gram-positive organisms and anaerobes. It inhibits bacterial growth, possibly by blocking dissociation of peptidyl transfer ribonucleic acid (t-RNA) from ribosomes, in that way causing RNA-dependent protein synthesis to arrest.

Vancomycin (Vancocin, Vancoled)

Vancomycin is used for the treatment of infections due to suspected or documented MRSA and for the treatment of serious or life-threatening infections due to S aureus.