Symptom-Based Diagnosis in Pediatrics (CHOP Morning Report) 1st Ed.

CASE 16-4

Two-Year-Old Boy

JEANINE RONAN

HISTORY OF PRESENT ILLNESS

A 2-year-old boy was well until 2 days prior to admission, when he slipped and fell on his right side. After the injury, the parents stated that he began limping. Later that evening he developed fevers to 103°F. He was treated with ibuprofen. During the course of the night he became irritable, particularly when his parents attempted to carry him. He refused to stand. He was taken to a nearby emergency department for evaluation. Radiographs of the right lower extremity were negative and he was sent home with the diagnosis of a knee contusion. The following day, he was able to walk for brief periods but continued to limp. However, during the course of the next few hours, he again stopped walking and became very clingy. He was taken to the hospital for reevaluation.

MEDICAL HISTORY

This child was a healthy boy with no significant medical history. His immunizations were up-to-date. His developmental history was also normal.

PHYSICAL EXAMINATION

T 38.3°C; RR 24/min; HR 110 bpm; BP 98/75 mmHg; Height 25th percentile; Weight 50th percentile

On physical examination, the child was crying and difficult to console. Heart, lungs, and abdomen were normal. There was mild swelling and erythema of the right lower extremity. There was significant tenderness over the length of the tibia. Range of motion was normal at the hip, knee, and ankle. Deep tendon reflexes were present. Perfusion to the right foot was normal. He would only walk with assistance, but he was able to crawl.

DIAGNOSTIC STUDIES

The complete blood count revealed a WBC count of 17 400 cells/mm3 (18% band forms, 77% segmented neutrophils, and 5% lymphocytes), a hemoglobin of 10.7 g/dL, and a platelet count of 578 000/mm3. The erythrocyte sedimentation rate (ESR) was 75 mm/h and his C-reactive protein (CRP) was 9.2 mg/dL. A blood culture was obtained. Repeat radiograph of the right tibia was normal.

COURSE OF ILLNESS

MRI of the right lower extremity confirmed the diagnosis (Figure 16-3).

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FIGURE 16-3. MRI of the tibia.

DISCUSSION CASE 16-4

DIFFERENTIAL DIAGNOSIS

Diagnosing the cause of limp or refusal to walk in a toddler is challenging. A history of overt trauma may be absent or, as in this case, the history of trauma may be misleading. Furthermore, localizing pain in young children may be difficult and the location of the pain may not accurately represent the area of pathology. In these children, the differential diagnosis can be narrowed by assessing associated symptoms. In this child who also has fever, infectious causes must be considered. Septic arthritis is unlikely given the normal examination of the hip, knee, and ankle joints. However, osteomyelitis remains a concern, particularly with associated leg swelling. Cellulitis and myositis are also possible. In addition, one should also consider that this could be the presentation of neoplasms including leukemia, neuroblastoma, or osteoblastoma. Rheumatologic diseases will also present with joint pain and fever. These may include juvenile idiopathic arthritis, reactive arthritis, and acute rheumatic fever.

DIAGNOSIS

MRI of the lower extremity revealed significant soft tissue swelling (Figure 16-3). There was mixed low signal along the entire diaphysis of the tibia consistent with small subperiosteal abscesses surrounded by edema. Edema was also seen circumferentially along the fascia consistent with fasciitis. These findings indicated extensive osteomyelitis of the entire tibia, as well as one large and numerous small subperiosteal collections. Neither the knee nor ankle joint was involved. Staphylococcus aureus was isolated from the initial blood culture. The diagnosis was acute hematogenous osteomyelitis of the tibia due to S. aureus. In this case, the diagnosis was suspected based on a combination of findings including swelling, erythema, and tenderness over the tibia. The elevated ESR and CRP supported the diagnosis. The MRI confirmed the diagnosis. Initially, the patient was treated with vancomycin based on local resistant patterns for community-acquired methicillin resistant S. aureus (CA-MRSA). With clinical improvement, including resolution of fever, being able to weight on his right leg and a substantial decrease in the CRP, the patient was switched to oral clindamycin once antibiotic susceptibilities were available. He was discharged on the sixth day of hospitalization to complete 3-4 weeks of oral antibiotic therapy based on the results of subsequent inflammatory markers. The CRP peaked on the second day after antibiotics were initiated and was normal by the seventh day of treatment. The ESR peaked on the fifth day and normalized 3 weeks after initiation of antibiotics.

INCIDENCE AND EPIDEMIOLOGY

Osteomyelitis in young children is usually due to hematogenous spread of bacteria. Most cases occur within the first 5 years of life, probably due to the rich vascular blood supply at the sites of rapid growth near the growth plates. The valveless sinusoids in the venules at the epiphysis will result in slow nonlaminar blood flow. It is hypothesized that trauma may lead to a hematoma and will be seeded by bacteria during episodes of asymptomatic bacteremia.

In order of decreasing frequency, the affected bones include the femur, tibia, humerus, fibula, and pelvis. The most common organisms causing osteomyelitis vary by age. In neonates, S. aureus, group B Streptococci, and enteric Gram-negative bacteria predominate. In infants and toddlers, S. aureus is by far the most common, but infections may occur due to pneumococcus, group A Streptococcus, and Kingella kingae. Fungal osteomyelitis due to Candidaspecies occurs in premature neonates and intravenous drug abusers. Tuberculous osteomyelitis, due to hematogenous or lymphatic dissemination, occurs in less than 1% of children with active tuberculosis. The spine, femur, and small bones of the hand and feet may be involved with tuberculous osteomyelitis.

Nonhematogenous osteomyelitis usually develops from open fractures, decubitus ulcers, implanted orthopedic equipment, or puncture wounds. Implantable equipment can become infected with S. aureus and coagulase-negative staphylococci. In the case of puncture wounds through sneakers, Pseudomonas aeruginosa and S. aureus are likely pathogens.

CLINICAL PRESENTATION

The presenting signs and symptoms in children with osteomyelitis depend on the site of infection. The typical presentation for patients with osteomyelitis is fever, bone pain, and the inability to bear weight. In many cases, there may be a history of past trauma. Trauma is believed to be a risk factor because of the increase in blood flow to the injured area that occurs after an injury.

Systemic symptoms include fever, malaise, and poor appetite. On physical examination, there may be swelling and erythema of the affected extremity. Often there is point tenderness rather than diffuse bone tenderness. In most cases, the metaphysis of the long bones are the sites of infection. Range of motion should be intact, in comparison to patients with septic arthritis in which micromotion tenderness will be seen. However, the patients may have some limited mobility due to pain or muscle spasm.

A septic hip and shoulder can result in osteomyelitis coinfection, since these joint capsules insert distal to the epiphysis on the femur and humerus. Neonates are unique in that vascular channels extend across the epiphyseal growth plates; thus an osteomyelitis can cause an adjacent joint infection.

DIAGNOSTIC APPROACH

In general, laboratory data may be helpful in supporting the diagnosis of osteomyelitis.

Blood culture. Blood cultures demonstrate the responsible organism in up to 50% of cases. It should be obtained in all cases of suspected osteomyelitis; it should also be obtained prior to the initiation of antibiotics when possible.

Complete blood count. The peripheral white blood cell count can be normal or elevated. It is neither sufficiently sensitive nor specific to aid in diagnosing osteomyelitis. If symptoms have been present for several days, thrombocytosis may also be present.

Inflammatory markers. CRP is elevated at presentation in over 95% of cases. The ESR is elevated in at least 90% of cases at presentation. If the CRP and ESR remain normal for 3 days in a patient with bone pain, the likelihood that the patient has acute osteomyelitis is low. The CRP and ESR can also be used to monitor response to antibiotic therapy. The CRP typically peaks 2 days after initiation of appropriate antibiotic therapy and returns to normal within 7-10 days. The ESR typically peaks by the fifth day after initiation of antibiotics and returns to normal 3-4 weeks later.

Bone biopsy or aspiration of subperiosteal collections. The gold standard for diagnosis is to collect bone aspirate for culture. In 80% of cases, an organism is identified from either the blood, bone, or joint fluids.

Radiologic studies. A plain radiograph will show lytic lesions and periosteal elevation approximately 10-14 days from the onset of symptoms. Radiographs taken before 14 days may be read as normal and should not divert the physician from pursuing the diagnosis.

A technetium-99m-methylene diphosphonate bone scan localizes to areas of hyperemia and early bone resorption. Images are obtained during three time periods: (1) during isotope infusion; (2) 5 minutes after injection (“blood pool” phase) when the isotope has pooled inflamed tissues because of the increased blood flow; and (3) 3 hours later (“bone” phase) after the isotope has left the soft tissues but remains in areas of bone remodeling. Cellulitis causes uptake in the first two phases while osteomyelitis causes update in all three phases. Bone scans may be most helpful in the following situations: (1) vertebral or pelvic osteomyelitis, (2) neonates, toddlers, and other children who may have difficulty localizing pain, and (3) multifocal involvement. While the sensitivity of the bone scan is high (80%-95%, though lower in neonates), it does not delineate the anatomy and cannot differentiate between trauma, fracture, infection, and infarction. Therefore, the specificity of the technetium bone scan is low.

MRI is the test of choice for diagnosing osteomyelitis with a sensitivity of 92%-100%. It is most useful when symptoms are localized to a specific region. To obtain this study in infants, toddlers, and young children sedation is required.

TREATMENT

Appropriate antibiotic selection depends on many factors including the patient’s age, mechanism of acquisition, and local susceptibility patterns for S. aureus, because this is the preeminent pathogen in 70%-90% of all cases (Table 16-7). For neonates with osteomyelitis, appropriate therapy includes the combination of an agent for S. aureus and a third-generation cephalosporin to treat Gram-negative infections and group B Streptococcus. In older children, therapy is directed at CA-MRSA and depending on local resistance patterns may include oxacillin, clindamycin, or vancomycin. Children with underlying hemoglobinopathies should receive cefotaxime or ceftriaxone empirically in addition to clindamycin or vancomycin given the high-risk for S. aureus and Salmonella. Additional antibiotics can be added to these regimens based on clinical presentation and mechanism of infection. Definitive therapy should be based on clinical response and culture results.

TABLE 16-7. The microbiology of osteomyelitis and empiric therapy.

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Response to therapy can be monitored by checking serial CRP and ESR levels. The CRP peaks on the second day after initiation of appropriate antibiotic therapy and returns to normal between the seventh and ninth day. Failure of the CRP to substantially decrease by the fourth day of therapy, raises the concern for treatment failure and may require reimaging or changing antibiotic therapy. The ESR generally peaks on the fifth day after initiation of antibiotics and returns to normal by the third or fourth week. Generally, the CRP and ESR are monitored on a weekly basis until therapy is completed.

Typically, therapy continues for 3 weeks and up to 6 weeks in more extensive cases. Duration of therapy depends on the causative organism, severity of illness, and clinical and laboratory response. Historically, treatment of S. aureus bone infections for less than 4 weeks led to an unacceptably high rate of relapse. Recent data support that this is not necessary. In addition, recent data have supported that early transition to oral therapy is just as effected as prolonged intravenous therapy. In addition, oral therapy is not associated with the risks of central venous catheters including infections and blood clots. When the CRP is decreasing and the signs of acute inflammation have improved including resolution of fever and ability to weight bear, oral therapy may be used. The willingness of the child to take oral medications and the ability of the parents to administer multiple daily doses must also be taken into account.

SUGGESTED READINGS

1. Conrad D. Acute hematogenous osteomyelitis. Pediatr Rev. 1995;16:380-384.

2. Roine I, Arguedas A, Faingezicht I, Rodriguez F. Early detection of sequelae–prone osteomyelitis in children with use of simple clinical and laboratory criteria. Clin Infect Dis. 1997;24(5):849-853.

3. Peltola H, Unkila-Kallio L, Kallio MJ. Simplified treatment of acute staphylococcal osteomyelitis of childhood. Pediatrics. 1997;99:846-850.

4. Jacobs RF, McCarthy RE, Elser JM. Pseudomonas osteochondritis complicating puncture wounds of the foot in children: a 10-year evaluation. J Infect Dis. 1989;160(4):657-661.

5. Paakkonen M, Kallio M, Kallio P, Peltola H. Sensitivity of ESR and CRP in childhood bone and joint infections. Clin Orthop Relat R. 2010;468(3):861-866.

6. Zaoutis T, Localio A, Leckerman K, Saddlemire S, Bertoch D, Keron R. Prolonged intravenous therapy versus early transition to oral antimicrobial therapy for acute osteomyelitis in children. Pediatrics. 2009;123(2): 636-642.

7. Peltola H, Paakkonen M, Kallio P, Kallio MJ. Osteomyelitis-Septic Arthritis Study Group. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Pediatr Infect Dis J. 2010;29:1123-1128.