A 5 year old male presents with decreased appetite and intermittent tactile fever for the last five days. He complains of pain in his right leg and he has been having an increasingly difficult time walking over the last 2 days. He has a history of falling seven days ago. His mother denies reports of recent weight loss, cough, or dysuria. He has no previous medical problems.
Exam: VS T 39.4, P 110, R 16, BP 95/50, oxygen saturation 99% RA. He is alert and non-toxic appearing. His heart, lungs and abdomen are normal. Examination of his extremities reveals swelling, warmth and tenderness to his right proximal tibia. He has some palpable inguinal lymphadenopathy on the right. He has difficulty bearing weight and walks with a slight limp. There are no cutaneous skin lesions. His neurologic and joint exams are non-contributory.
Laboratory studies show WBC 18,000, 68% segs, 7% bands, 20% lymphs, 5% monos, H/H 13.4/40, Platelet count 290,000. ESR 60 and CRP 15. Plain radiographs of his right tibia and fibula are normal. An MRI scan shows a hyperintense signal in the marrow with a small pocket pus elevating the periosteum and soft tissue swelling of the right proximal tibia suggestive of osteomyelitis.
An orthopedic consultation is obtained, and a closed needle drainage of the area is done. IV vancomycin is started and subsequent blood and wound cultures grow out methicillin sensitive Staphylococcus aureus. His antibiotics are changed from vancomycin to oxacillin. While in the hospital, his fever declines and his function returns. He is discharged on oral antibiotics to complete four weeks of treatment.
Osteomyelitis by definition is inflammation of the bone. The annual incidence of acute osteomyelitis is about 1/5000 children under 13 years old (1). This disease appears to affect males more often than females, and the majority of the cases occur in patients less than 20 years old. The most common cause of osteomyelitis is bacterial; however, fungal and viral causes are also possible.
Acute bacterial osteomyelitis can be thought of in three different categories: 1) hematogenous seeding, 2) contiguous spread, and 3) direct inoculation of the bone either from surgery or trauma. Of the three categories, acute hematogenous osteomyelitis is the most common presentation in children. Acute hematogenous osteomyelitis has a predilection for the long bones of the body. Long bones consist of two distinct types of bone. The diaphysis or shaft is made of a dense lamellar bone, which is relatively acellular and slow growing. The ends of the bone near the growth plate (the metaphysis) is made of a maze like bone called cancellous bone. This maze like structure allows for spreading of the infection via small channels in the bone that leads into the subperiosteal space. It is here in the rapidly growing metaphysis that osteomyelitis often develops. The process begins when thrombosis and bacterial emboli transmigrate through the end capillaries as a result of local trauma or stasis of local blood flow. This results in bacterial seeding creating a nidus for infection that can be difficult to remove due to a relative lack of reticuloendothelial cells. Pus collects in the subperiosteal space and surrounding edema produces a mass effect that further decreases blood flow perpetuating tissue ischemia and necrosis. Isolated pieces of dead bone, or sequestrations can result from this process. As the remodeling process continues, an involucrum can be created when new bone is deposited over an area of dead bone. The pathophysiology of osteomyelitis differs slightly by age group. In neonates, blood flow from the metaphysis is continuous with the joint space and thus a concurrent septic arthritis may develop. Furthermore, in this age group the periosteum is thinner and thus more likely to rupture into surrounding tissue. This is in contrast to older children in which the infection is contained due to a well developed periosteum resulting in focal physical findings.
The signs and symptoms of acute osteomyelitis may be subtle, especially in the very young. The chief complaint of a child suspected of having osteomyelitis may be refusal to walk and bare weight on the affected limb, or the refusal to utilize a specific body part. Often a recent history of upper respiratory symptoms or trauma is elicited. The very young infant may present with only a history of a poor appetite and fever, or be ill appearing in fulminate septic shock. Objective findings are fever, swelling, point tenderness, and erythema of the affected body part. The child may have a pseudoparalysis of the affected limb. The most common long bones involved in descending order are the femur, tibia, humerus, fibula, radius and ulna (2). Flat bones are affected less than 20% of the time; of these the calcaneus and pelvic bones are the most common and about equal in incidence (2). Occasionally the physical findings are very subtle, such as a loss of natural body curvatures or normal skin creases. Thus, examination of the opposite side for symmetry is an important aspect of the physical exam. Lastly, assessment of the patient's gait for a limp may also help to make the clinical diagnosis.
Laboratory studies are helpful in making the diagnosis of osteomyelitis. The most useful laboratory values are the acute phase reactants, the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). These values are often highly elevated in the presence of acute osteomyelitis, and are non-specific indicators of acute inflammation. The ESR is determined by the rate that red blood cells fall through plasma. This value is dependent on the content of fibrinogen in the blood. The value for ESR usually starts to increase at about 48-72 hours from the start of the infection process. CRP is a protein created by the liver. The theoretical advantage to CRP is that it is said to rise earlier than the ESR, about six to ten hours after the onset of inflammation. It also declines much more rapidly after initiation of therapy, and thus may be a good way to monitor therapeutic efficacy (3). The white blood cell (WBC) count has been found to be unreliable in diagnosing acute osteomyelitis (4). Often, a normal WBC count may be misleading to the clinician in the presence of osteomyelitis. Despite this fact, a CBC can be helpful to rule out other diagnoses, and thus it is an integral part of the workup. Bacterial cultures, when positive, are very helpful in the diagnosis and management of acute osteomyelitis. Blood cultures have been reported to be positive 30-50% of the time (4). Sterile needle aspiration of the affected area yields an organism about 60% of the time if pus is attained (4). Identification of the offending organism and antibiotic sensitivities is an extremely important aspect to guide therapy. The most common organism isolated is Staphylococcus aureus (70-90%) (2). This is followed by group A Streptococcus, Streptococcus pneumonia, and Haemophilus influenza (2). Salmonella and other enteric pathogens must be considered in patients with sickle cell disease. In the newborn period, group B Streptococci, Escherichia coli, and Staphylococcus epidermis are often the cause of osteomyelitis. Lastly, Pseudomonas aeruginosa is a common cause of infection due to plantar puncture wounds that are sustained through sneakers.
Radiographic imaging is an important component in making the diagnosis of osteomyelitis, and should always start with plain radiographs of the affected area. Despite the fact that plain radiographs will only begin to show osteogenic changes five to seven days into the disease process, plain radiographs are helpful to rule out other etiologies of bone pain. A nuclear medicine bone scan is a very sensitive test to diagnose osteomyelitis. This procedure is done in three phases, and utilizes technetium 99m to create images that determine areas of infection and bone remodeling dependent on local blood flow. The sensitivity of the bone scan is high (>90%), and this test is often helpful when the exact location and extent of the infection in the body is unknown (5). CT scanning allows for three dimensional examination of bone and the surrounding soft tissues. This imaging modality can help to show periosteal reaction, cortical bone destruction and if any sequestration or involucrum is present (5). Ring enhancing soft tissue abscesses can also be found. Magnetic resonance imaging (MRI) is an extremely useful imaging modality in acute osteomyelitis. Findings on MRI accurately illustrate the extent and structure of the area involved in the pathologic process. Sensitivity has been reported to be 88-100% with a specificity of 75-100% (5). Fat suppression sequences allow for better detection of bone marrow edema; however, this cannot differentiate between infection and inflammation (5). MRI may be the imaging modality of choice for infections involving the spine, pelvis, and limbs due to its ability to provide fine details of the osseous changes and soft tissue extension in these areas. MRI does have the disadvantages of high cost and requiring sedation for young children.
The differential diagnosis of a child who presents with fever, bone pain and tenderness includes rheumatic fever, septic arthritis, cellulitis, Ewing sarcoma, osteosarcoma, neuroblastoma, leukemia, thrombophlebitis, bone infarction due to sickle cell disease, and toxic synovitis.
The mainstay of treatment focuses on eradication of the offending organism and the minimization of tissue damage. The first is accomplished through initiating parenteral antibiotics. In the older child, the focus is against the more common gram positive organisms (S. aureus and group A Streptococci). A beta lactamase resistant penicillin (oxacillin, methicillin or nafcillin) or a cephalosporin will cover Group A Strep, but only 70% of Staph aureus. Thus, these antibiotics are unacceptable coverage since the risk of resistance is too high. All patients should be started empirically on vancomycin. In the younger child and patients with sickle cell anemia, gram negative pathogens such as Haemophilus and Salmonella must be considered, thus the addition of ampicillin or a third generation cephalosporin (cefotaxime or ceftriaxone) is important. The duration of treatment is somewhat controversial; however it appears that at least four to six weeks is required. Shorter courses have shown to have an increased incidence of recurrence (2). Peripherally inserted central IV catheters can be placed and home antibiotics can be arranged with home care. Recently, oral antibiotics have become an accepted option to complete therapy. However, the following criteria must be met: organism identification (with sensitivities), the ability to take and keep down oral antibiotics, a clear response to parenteral treatment, and assured routine compliance (4). Often, the dose of oral agents is two to four times the normal dose to maintain adequate drug levels. MIC and MBC (minimum inhibitory and minimum bactericidal concentrations) data may be useful in predicting a therapeutic success. Following laboratory results such as the CBC, CRP and ESR at routine intervals may be helpful to monitor clinical progress and monitor iatrogenic side effects.
Surgical debridement helps to decrease the tissue damage that occurs due to the inflammatory reaction caused by the infection. The removal of the inflammatory products allows for a more optimal environment to maximize the efficacy of medical therapy. Two criteria that help to make the decision to perform surgical debridement are the ability to aspirate pus from the lesion and a failure to see a clinical response within 36-48 hours of the initiation of medical treatment (4). Samples attained from debridement should be sent for pathology identification, cultures and antibiotic sensitivity.
Chronic osteomyelitis can occur due to a penetrating injury/inoculation or inadequate therapy (often due to non-compliance with outpatient antibiotics). This poses an extremely complicated medical and surgical task for the clinician. Like in acute osteomyelitis, Staph aureus is often the organism isolated by culture. However, chronic osteomyelitis has a higher incidence of gram negative rods, anaerobes, and non-bacterial pathogens such as fungus and yeast. Very long term antibiotic therapy and repeat surgical interventions may be required (with occasional amputation), and recovery is long and complication prone. The prognosis for a normal outcome with chronic osteomyelitis can be poor.
1. True/False: The most common pathogen in acute hematogenous osteomyelitis is Group A streptococci.
2. True/False: A sequestration is an area of loose necrotic bone that is a result of acute osteomyelitis.
3. True/False: The duration of antibiotic therapy for acute hematogenous osteomyelitis is typically 7-10 days.
4. True/False: Two clinical conditions for surgical intervention in acute osteomyelitis are the ability to aspirate pus from the lesion and a lack of response to medical treatment in 36-48 hours.
5. True/False: Plain X-rays will always show bony changes within the first few days of the onset of acute osteomyelitis.
6. True/False: The most common bone involved in acute hematogenous osteomyelitis in children is the tibia.
7. True/False: Osteomyelitis has a propensity to involve the diaphysis of the long bones.
8. True/False: Since Staph aureus is the most common organism involved in osteomyelitis, initiating therapy with an anti-Staph aureus penicillin such as oxacillin is generally accepted as adequate.
1. Sonnon G, Henery N. Pediatric Bone and Joint Infections. Pediatr Clin North Am 1996;43(4):933-947.
2. Krogstad P, Smith A. Chapter 64: Osteomyelitis and Septic Arthritis. In: Feigin RD, Cherry JD (eds). Textbook of Pediatric Infectious Disease, 4th edition. 1998, Philadelphia: W.B. Saunders Co., pp. 683-698.
3. Unkila-Kallio L, Kallio M, Eskola J, Peltola H. Serum C-Reactive Protein, Erythrocyte Sedimentation Rate, and White Blood Cell Count in Acute Hematogenous Osteomyelitis of Children. Pediatrics 1994;93(1):59-62.
4. Morrissy RT. Chapter 13: Bone and Joint Sepsis. In: Morrissy RT, Weinstein SL (eds). Lovell and Winter's Pediatric Orthopaedics, 5th edition. 2001. Philadelphia: Lippincott Williams and Wilkins. p 459-500
5. Oudjhane K, Azouz E. Imaging of Musculoskeletal and Spinal Infections. Radiol Clin North Am 2001;39(2):251-266.
Answers to questions
1. False. S. aureus is the most common. Group A strep is the second most common.
3. False. Typically the course is for 6-8 weeks, always starting with IV antibiotics and finishing with PO antibiotics if possible.
5. False. Plain films usually begin to show acute changes 5-7 days into the course of the disease process.
6. False. The femur is the most commonly involved bone. The tibia is the second most commonly involved.
7. False. The metaphysis is the most common site.
8. False. The rate of methicillin resistant S. aureus is too high to use oxacillin/methicillin as empiric therapy. Vancomycin should be initially started.