Osteomyelitis (Pediatric)

Introduction

Infections of the musculoskeletal system in children - osteomyelitis and septic arthritis - comprise a broad spectrum of disorders that vary greatly in severity and complexity. Appropriate and timely workup is needed to yield an accurate diagnosis and enable prompt treatment to improve clinical outcomes. Simply defined, osteomyelitis is an infection of bone whereas septic arthritis is an infection of a joint. Most cases of these conditions occur from a common source: hematogenous inoculation via the metaphyseal circulation. Here, blood flow is sluggish, allowing bacteria (present in the transient bacteremia common in children) to linger. If the bacteria remain in the bone, osteomyelitis may result; if they exit the periosteum septic arthritis may ensue, as the metaphyseal region is often within the joint capsule. Additionally, direct inoculation from penetrating trauma or surgical procedures may also initiate the process.

Osteomyelitis can be considered to have four distinct forms: Acute Hematogenous Osteomyelitis (AHO); Subacute Osteomyelitis; Chronic Osteomyelitis; and Chronic Recurrent Multifocal Osteomyelitis.

Acute Hematogenous Osteomyelitis (AHO)
Children with AHO by definition develop symptoms acutely and usually are evaluated within the first several days of the onset of their condition. The acute, focal bone pain is often, but not always, accompanied by systemic findings of fever or malaise. It is important to consider the most relevant conditions in the differential diagnosis like trauma, leukemia, malignant tumors such as Ewing's sarcoma or osteogenic sarcoma, and bone infarction from sickle cell crisis. This condition is most similar to septic arthritis in its presentation

Subacute Osteomyelitis
Children with subacute osteomyelitis develop a gradual and insidious type of extremity pain without signs of systemic illness. The pain has usually been present for at least two weeks, but possibly for months. Laboratory studies are often unremarkable, although the ESR may be elevated. The condition is believed to result from an altered host-pathogen relationship, either from a decrease in bacterial virulence or an increase in host resistance. Alternatively, subacute osteomyelitis may be the result of a partially treated case of AHO.

Chronic Osteomyelitis
The classic features include the presence of dead bone (sequestrum) often surrounded by gross purulence and reactive new bone (involucrum). Draining sinuses may erupt as the rapid expansion of infection erodes through overlying tissue planes. The principles of treatment include surgical debridement of all necrotic tissue, leaving behind viable bone and periosteum, and identification of the causal organism to ensure that the most appropriate antibiotic is selected for long-term intravenous treatment. Attempts to reconstruct should usually be made after the infection has resolved.

Chronic Recurrent Multifocal Osteomyelitis (CRMO)
CRMO is a condition of insidious onset involving multiple bone locations associated with pain and malaise. There is a reported association with palmo-plantar pustulosis. The radiographic findings and histology, if obtained, are suggestive of osteomyelitis. However, cultures of bone and blood are negative and antibiotics have not been found to be necessary in treatment. Overall, the disease is considered benign and self-limited.

Epidemiology

The vast majority of these infections are bacterial, with Staphylococcus aureus currently isolated as the most common causative organism in all age categories. Other organisms frequently involved in pediatric musculoskeletal infections are listed in Table 1.
The peak incidence of joint infections occurs during the first 5 years of life, whereas that for bone infections occurs between the ages of 5 and 10 years.

Table 1: Common Causative Organisms and Empiric Antibiotic Selection for Septic Arthritis or Osteomyelitis According to Age

Clinical Evaluation

The need for a complete history and physical examination is unfortunately often unmet: the limited ability of small children to communicate and cooperate with an examination interferes. Thus there is a tendancy to rely on laboratory or radiologic data to establish a diagnosis. However, the clinical examination and history remain paramount in the evaluation process.

Relevant historical questions - for the parents or caregivers - include:

• time of onset,
• nature and location of symptoms,
• presence of constitutional symptoms,
• recent infection or treatment with antibiotics,
• refusal to walk or bear weight,
• trauma,
• foreign travel, and
• known recent or remote exposure to infectious disease.

Relevant physical findings which should be sought include:

• focal tenderness,
• warmth,
• erythema,
• swelling,
• limited range of motion,
• pseudo-paralysis,
• limp,
• synovitis, rash or
• joint effusion.

Laboratory Evaluation

The studies which should be obtained initially include a complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and blood cultures. Other studies which may be considered when the clinical history or physical examination raise concern are listed in Table 2 along with the indications for obtaining these studies.

Elevation of the ESR is a non-specific finding and may occur in a variety of inflammatory conditions. In response to infection, however, the peak ESR has been shown to occur within 3-5 days of the onset with mean values of 58 mm/hr.

Sequential determination of the CRP is perhaps the most important laboratory test used in evaluating and treating musculoskeletal infection. The serum value begins to rise within 6 hours of the triggering stimulus and increases several hundred-fold, reaching a peak within 36-50 hours of onset.

Unfortunately, Blood cultures yield positive results in only 30-50% of cases of both septic arthritis and osteomyelitis. However, they are indispensable as they not only establish the diagnosis of infection in general, they may isolat and indetify the organism and thus serve as a guide to treatment. It is preferable that no antibiotics be administered prior to obtaining proper cultures.

Table 2. Indications for Selected Additional Studies in Workup for Infection

Procedural Evaluation

Aspiration

Aspiration has the greatest yield for diagnosis in cases of suspected septic arthritis. Although exceptions exist, cell counts greater than 80,000/mL with greater than 75% PMN's suggest infection, while those less than 15,000/mL with less than 25% PMN's suggest inflammation from other causes.

Bone aspiration in cases of suspected osteomyelitis may provide the only means for obtaining a positive culture and therefore should be considered prior to initiating antibiotics.
Aspiration can be performed safely with sterile technique and intravenous sedation.

Radiology

Plain Radiography

High quality plain radiographs are essential in all cases of suspected musculoskeletal infection. At minimum, anteroposterior and lateral projections of both the involved and uninvolved extremities should be performed with a technique which allows for visualization of the deep soft tissues. Deep soft tissue swelling is the first radiographic manifestation of musculoskeletal infection. Changes in the bone secondary to osteomyelitis may not occur for one or two weeks after the onset of infection.

Ultrasound

The usefulness of ultrasound in evaluating bone and joint infections is often overlooked in light of the availability of nuclear medicine and magnetic resonance imaging (MRI). The advantages of ultrasound include low cost, avoidance of radiation exposure, non-invasive nature without the need for sedation, ability to detect and localize joint fluid for aspiration in the hip, and ability to detect the early changes in the deep soft tissues in osteomyelitis. Ultrasound is also useful in identifying abscess of the psoas muscle, which may present a confusing clinical picture.

Nuclear Medicine

Technetium 99m diphosphonate scanning is one of the most commonly used techniques to evaluate the skeleton for increased activity suggestive of infection. The study consists of three phases: blood flow (essentially a radionuclide angiogram performed immediately following injection), blood pool (performed after a brief period to evaluate soft tissue pooling) and delayed images (performed 2 to 3 hours later to evaluate the calcium phosphate deposition in bone). Gallium-67 citrate imaging has been proposed as a useful adjunctive study in cases when the technetium bone scan is normal.

Magnetic Resonance Imaging (MRI)

MRI is a powerful diagnostic tool for the evaluation of musculoskeletal infections. Characteristics of infection seen on MRI include dark marrow on T1-weighted images and increased marrow signal intensity on T2-weighted images. Abscess formation or subperiosteal fluid collections may also be identified as bright signal on T2-weighted images.

Treatment

The goal of treatment is the eradication of the bacteria. This requires delivery of an appropriate concentration of the correct antibiotic to the site of infection for an adequate duration of time.

The issue of delivery is made complex by the fact that the blood supply to all of the infected area is poor, especially in the case of a sequestrum. Appropriate concentrations of drug may require parenteral administration. The correct antibiotic may be chosen empirically but one can be sure of its correctness (including the susceptibility of the bacteria to it) by obtaining a sample and isolating the bacteria in culture. Completing a course of adequate duration often involves secondary considerations such as cost, convenience to family and physician, and compliance.

Traditional use of four or six weeks of parenteral antibiotics for septic arthritis or osteomyelitis, respectively, have been frequently challenged to allow for less expensive and more convenient alternatives with equal efficacy.

Antibiotics
The importance of properly identifying the causative organism and assessing its sensitivity to specific antibiotics cannot be overstated. Although empiric selection can be relied on to adequately treat the most common organisms in each age category (Table 1), there is obviously much greater confidence that the antibiotic selected has the appropriate spectrum of coverage if an organism is identified.

Route
Oral antibiotic administration is less expensive and more convenient than intravenous administration. However, while it is possible to establish adequate serum, bone, and joint bactericidal concentrations by oral means, several considerations may favor parenteral treatment. During the initial treatment period, when close monitoring of the clinical and laboratory response is necessary, intravenous antibiotic delivery is essential. Subsequently, it should be determined whether or not there are any specific contraindications to oral therapy.

Duration
Generally, joint infections require a shorter treatment course than bone infections. The possibility of chronic infection of bone necessitates a longer period to ensure eradication of disease. Generally, the duration of antibiotic therapy for uncomplicated osteomyelitis is approximately six weeks and that for uncomplicated septic arthritis is approximately four weeks. Close clinical and laboratory monitoring during the treatment course is helpful in identifying patients that may benefit from longer duration of treatment or another alteration of the treatment regimen.

Surgery
Surgery often plays a key role in the early treatment of septic arthritis. However, the role of surgery in cases of osteomyelitis is less clear. Most children will respond well to medical treatment alone. Most would agree that in cases with radiographically demonstrable deep soft tissue or intra-osseous abscess formation surgical decompression is necessary to allow for clinical and laboratory improvement and eventual resolution of the infection. Some would suggest that if significant improvement has not resulted within 48 hours, regardless of radiographic evidence of abscess, then surgical exploration and decompression should be considered. Clearly, these decisions need to be made on a case by case basis, taking into account all clinical, laboratory, and radiologic information.

Special Considerations

Neonatal and Infantile Infections
Although the neonatal period is defined as the first 4 weeks of life, the pathogenesis of neonatal infections extends over the first 8 weeks. Neonatal infection can be considered in two distinct forms. The first occurs in premature infants who spend substantial time in the intensive care unit in the presence of nosocomial pathogens while undergoing frequent invasive procedures (including umbilical vessel catheterization) for intravenous access, monitoring, and hyperalimentation. Almost half of infants demonstrating sepsis under these circumstances will have multiple sites of infection. Therefore, a high index of suspicion should be maintained when there is any evidence of sepsis in the premature infant. Likely causative organisms includeStaphylococcus aureusand gram negative bacteria. Candida albicans may also be involved in those receiving prolonged broad-spectrum antibiotic treatment for sepsis. The second form of neonatal infection occurs in those term infants who have been routinely discharged from the hospital following their delivery. Manifestation of their musculoskeletal infection usually occurs between 2 and 4 weeks of life, but can occur up to 8 weeks after delivery. These infections are most commonly mono-articular and caused by group B Streptococcus. Antibiotic selection should be carefully considered in close communication with an infectious disease specialist and a neonatal intensivist, especially for hospital acquired sepsis. Hepatic and renal function as well as weight are important considerations in choosing the correct antibiotic and dose.

Sickle Cell Disease
The most common causative organisms areSalmonellaspecies andStaphylococcus aureus. Empiric antibiotic selection should cover both organisms until specific guidance from cultures is available. Cefotaxime or ceftriaxone are considered appropriate for this purpose.
The initial management of musculoskeletal pain in children with sickle cell disease should include oxygen, hydration, and analgesics. Failure to improve within 2 to 4 days along with fever and the appearance of systemic illness should elevate the possibility of infection as the underlying cause.

Significant Organisms

Group A Streptococcus
Group A Streptococcusis responsible for several types of musculoskeletal involvement in children. The most serious involves a toxic shock-like syndrome that is characterized by severe local tissue destruction and life-threatening systemic manifestations. Aggressive resuscitation is necessary along with timely surgical decompression of foci of infection in the musculoskeletal system following a vigilant search for such sites. Streptococcus pyogenesmay also cause osteomyelitis or septic arthritis by hematogenous inoculation in the absence of systemic shock.

Neisseria Meningitidis
While Neisseria meningitidisis not known for direct infection of the musculoskeletal system, it is significant as a causal organism in purpura fulminans which results in devastating musculoskeletal consequences. This disorder is characterized by the acute onset of progressive dermal vascular thrombosis, disseminated intravascular coagulation, and shock.
Treatment principles involve initial resuscitation efforts with appropriate antibiotics covering the causal organism, which isNeisseria meningitidisin the majority of cases. A third generation cephalosporin, such as cephtriaxone is usually effective.

Streptococcus Pneumoniae
While more commonly associated with pneumonia or meningitis,Pneumococcushas been reported in osteomyelitis and septic arthritis in children between the ages of 3 and 24 months. Although Streptococcus pneumoniaeis not an endotoxin-producing organism, thePneumococcalautolysin is thought responsible for playing this role.

Neisseria Gonorrhoeae
Pediatric patients are affected by gonococcal arthritis in three situations. The first occurs when the neonate contracts the disease passing through the birth canal in an infected mother. The second occurs as a result of sexual abuse in children or adolescents. The third occurs in sexually active adolescents. When gonoccal infection is suspected cultures should be obtained from the joint fluid, cervix of postpubertal girls, urethral or prostatic discharge of males, and additionally from the vagina, pharynx and rectum in children suspected to be victims of sexual abuse. BecauseNeisseria gonorrhoeaeis difficult to culture, special handling instructions are necessary to increase the potential of positively identifying the organism. Treatment of gonococcal arthritis involves local aspiration and irrigation of the joint and intravenous administration of a third generation cephalosporin due to the prevalence of resistant strains.

Mycobacterium tuberculosis
Tuberculosis infections have been increasing in incidence in the United States since 1985. Osteomyelitis, dactylitis, or septic arthritis may take one to three years to become manifest after the initial infection. Over half of all cases of tubercular osteomyelitis involve the spine, followed in incidence by infections around the hip and knee.
Spinal involvement usually occurs in the anterior one-third of the vertebral body. Paravertebral abscess and calcification is almost pathognomonic for spinal tuberculosis. Skeletal tuberculosis is associated with characteristic round cystic lesions in the epiphysis or metaphysis with centrifugal, ill-defined margins. Diagnosis requires a high index of suspicion with skin testing for tuberculosis using purified protein derivative and identification of the organism in culture material. The WBC is frequently normal, but the ESR is often elevated.
Current recommendations for the treatment of skeletal tuberculosis involves four drug therapy with isoniazid, rifampin, pyrazinamide, and streptomycin for two months followed by isoniazid and rifampin for an additional ten months. Surgical decompression of foci of infection is rarely necessary. Indications for spinal surgery include neurologic involvement, spinal instability, and failure of medical treatment.

Borrelia Burgdorferi (Lyme Disease)
Lyme disease, caused by the spirocheteBorrelia burgdorferi, was named after the Connecticut town in which it was first identified. The common vector is the deer tick. After inoculation, with a tick bite that may go unnoticed, the delay before systemic manifestations may be 2 to 30 days. The treatment initially consists of 10 to 30 days of oral antibiotic (amoxicillin or doxycycline). In cases of severe neurologic or cardiac manifestations or recurrence following oral therapy, intravenous ceftriaxone may be necessary for 14 to 28 days.
A post-Lyme disease syndrome has been described as recurrent arthralgias, myalgias, headache, neck pain, and fatigue. Treatment with antibiotics is controversial and spontaneous resolution within 6 months is common. Overdiagnosis of Lyme disease is a significant problem due to the inordinate attention which this condition has received in the media. Therefore, a careful workup should proceed according to the CDC recommendations.

Summary

Pediatric musculoskeletal infections are associated with a diverse presentation ranging in spectrum from obvious and acute to insidious and chronic. A thorough history and physical examination along with appropriately selected radiologic and laboratory studies should result in a timely and correct diagnosis most of the time. Vigilant evaluation will likely reduce diagnostic delay and adverse sequelae.