Emergency Department Management Of Acute Hematogenous Osteomyelitis In Children

Table of Contents

 

1. Abstract
2. Case Presentation
3. Introduction
4. Critical Appraisal Of The Literature
5. Etiology And Pathophysiology
6. Differential Diagnosis
7. Prehospital Care
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
9. Diagnostic Studies
   1. Peripheral Blood Investigations
   2. Imaging Studies
      1. X-Ray
      2. Ultrasound
      3. Computed Tomography
      4. Special Diagnostic Considerations
   3. Microbiologic Studies
10. Treatment
11. Special Circumstances
    1. Sickle Cell Disease
    2. Mycobacteria And Fungi
    3. Kingella kingae
12. Disposition
13. Summary
14. Risk Management Pitfalls For Acute Hematogenous Osteomyelitis
15. Clinical Pathway For Workup Of Suspected Acute Hematogenous Osteomyelitis
16. Clinical Pathway For Pharmacological Treatment Of Acute Hematogenous Osteomyelitis
17. Cost-Effective Strategies For Osteomyelitis
18. Case Conclusions
19. Tables and Figures
    1. Table 1. Most Common Etiologies Of Acute Hematogenous Osteomyelitis, By Age Group
    2. Table 2. Differential Diagnosis Of Acute Osteomyelitis
    3. Figure 1. Hematogenous Osteomyelitis Of A Tubular Bone In A Child
    4. Figure 2. Brodie Abscess
    5. Figure 3. Ultrasound Scan Of Subperiosteal Abscess
20. References

Abstract

Acute hematogenous osteomyelitis has an annual incidence of approximately 2 to 13 cases per 100,000 persons in developed countries. It can be difficult to diagnose in pediatric patients due to the condition’s often vague presentation. However, it is critical for the emergency clinician to be able to properly identify osteomyelitis, as it can have devastating consequences if left untreated. Because this is a relatively rare condition, there is limited evidence to guide the management, and there is a lack of standardized guidelines. In this issue, a systematic approach to the workup and treatment of a child who presents with possible acute hematogenous osteomyelitis is discussed. The most critical components of the history and physical examination, diagnostic studies, and treatment options are reviewed, including algorithms to guide management. Special populations are given consideration throughout the discussion, and management algorithms are provided.

Keyword: toxic hemoglobinopathies, hemoglobin, carbon monoxide, carboxyhemoglobin, sulfhemoglobin, methemoglobin, methylene blue, hyperbaric oxygen therapy, carboxyhemoglobinemia, sulfhemoglobinemia, methemoglobinemia

Case Presentation

An 8-year-old boy with a history of sickle cell disease presents to the ED on a weekday afternoon because he could no longer keep up with his teammates during soccer practice. His mother is very worried and tells you that he is “not walking right.” She had taken him to his pediatrician earlier in the week because of right leg pain and was told to give him ibuprofen as needed. As the week progressed, he has complained of increasing right leg pain, and later developed a limp. Today, he could not run with his teammates because the pain had worsened. His mother tells you that he felt warm on the way to the ED. The boy denies any trauma. He has not had any chest pain or pain elsewhere in his body, and the rest of his review of systems is negative. His physical examination is notable for a low-grade temperature and mild tachycardia. As he climbs onto the examination bed, you notice that he favors his left leg. He is tender to palpation over the distal aspect of his right femur with some swelling noted, and he begins crying as you palpate. He has full range of motion of his hips, knees, and ankles without any joint swelling or tenderness, and he has normal sensation and reflexes. The rest of his physical examination is normal, as well. You inform the patient and his mother that the differential diagnosis for this presentation is broad and further workup is needed. You tell her you will start with pain medication, x-rays, and blood work. As you think about all of the children you have seen with a limp, you narrow your differential diagnosis, considering the acute onset of this patient’s symptoms and the focal nature of his pain. Aside from plain films and blood work, you consider what else will be helpful for his workup. What specific lab tests might help you to make a diagnosis? In addition to the xray, should you order a CT scan, bone scan, or an MRI? If this is an infectious process, what antibiotics should you choose? Is the fact that he has sickle cell disease related to this presentation?

A previously healthy 2-month-old girl is brought to the ED for “crying all the time” for the past 3 days. Initially, her mother was unsure why her daughter was crying so much, but now she thinks it happens every time she changes her diaper. She feels that the crying is due to some kind of pain. She checked a rectal temperature at home prior to presenting to the ED, and she recalled that it was 38.6°C. On taking further history, you learn that the infant was born vaginally, full-term, and that her mother had no complications during pregnancy or delivery. Of note, her mother is a nurse at your hospital. On physical examination, the patient’s vital signs are notable for a fever to 38.9°C rectally. As you observe her lying on the examining table, you note that she is not moving her left leg. There is minimal swelling over her left calf, and she cries if you try to flex or extend her left knee. She has normal pedal pulses with good capillary refill. Her skin is intact, and the rest of her physical examination is normal. You inform her mother that you would like to perform some x-rays and order laboratory tests. As you think about her constellation of symptoms, you begin to form a differential diagnosis, likely with an infectious cause. What pathogens are likely to have caused this presentation? Is this related to her knee, and should you perform ultrasound on the knee joint? What are some other diagnoses you need to assess and rule out?

Introduction

Unrecognized osteomyelitis can have devastating consequences, such as sepsis, disruption of bone growth, and deformity.¹ To further complicate matters, presenting symptoms (including fever, irritability, or pseudoparalysis) can be nonspecific and difficult to localize.^2,3 These factors make it critical for every emergency clinician to be aware of when to suspect osteomyelitis and to know how to work up suspected osteomyelitis in children.

Acute hematogenous osteomyelitis (AHO) is defined as an infectious process in the bone lasting < 14 days. Chronic osteomyelitis, which occurs less commonly in children, is a process that lasts> 14 days, and is more often associated with trauma, foreign bodies, and neurologic disorders.⁴ In a recent systematic review of 132 published articles, the incidence of osteomyelitis in developed countries was found to be 1.94 to 13 per 100,000.1 The incidence has been reported to be higher in developing countries and in special populations. The highest reported incidence is among the Aboriginal peoples of Western Australia.5 In the largest prospective population-based multicenter study in Norway, Riise et al followed 429 patients referred to the hospital for signs and symptoms consistent with osteomyelitis.⁶ They found that the total annual incidence rate for acute osteomyelitis was 8 per 100,000 and that the incidence was higher for patients aged < 3 years. A review of multiple retrospective studies found the mean age to be 6.6 years old with a male-tofemale ratio of 1.82:1.⁷ The same review found that most cases of osteomyelitis had an unknown cause, though blunt trauma and recent systemic illness were noted to be significant risk factors in 29.4% and 37.4% of cases, respectively. It should also be noted that there is controversy regarding the incidence of osteomyelitis over time; some studies have reported a decrease, while others have reported an increase. Gillespie et al examined hospital data over a 17-year period (from 1965 to 1982) in 4 different countries (Australia, New Zealand, England, and Scotland) and found a significant decline in 4 of the 6 populations studied and no trend in the other 2 populations.⁵ Blythe et al reported a decline in the incidence of acute and subacute osteomyelitis of 44% from 1990 to 1997 in children aged < 13 years.⁷ In contrast, Malcius et al examined data over a 21-year period (from 1982 to 2003) and found an increase in the incidence of AHO among children in Lithuania.⁸

Osteomyelitis in children usually involves long bones, and the femur and tibia are the most commonly involved.¹ This condition can also occur in the pelvis⁹ and vertebrae. Vertebral osteomyelitis should be considered as a differential diagnosis for any patient presenting with back pain. Certain populations, such as those with sickle cell disease, are at higher risk for osteomyelitis. All patients with sickle cell disease are at higher risk of various types of infection due to increased bone marrow turnover, poor perfusion, and functional asplenia.¹⁰ Additionally, these patients tend to have prolonged and more severe osteomyelitis, partly due to microvascular disease and bone infarction.¹¹ They frequently have different causative pathogens and more commonly present with multifocal disease.^11,12 Salmonella species are the most common etiology of AHO in this population, but Staphylococus aureus and other enteric gram-negative bacilli are also important pathogens.

Evidence-based clinical practice guidelines for osteomyelitis are not only helpful to the emergency clinician, but also to every provider taking care of a child with osteomyelitis. This was recently highlighted in an article by Copley et al. This group developed and implemented clinical practice guidelines with input from several departments and services (including pediatrics, orthopedics, infectious disease, and social work). After implementation of the practice guidelines, patients had fewer antibiotic changes, a shorter hospital stay, and a lower readmission rate.¹³

Critical Appraisal Of The Literature

A systematic search of published literature from 1970 to June 2013 was undertaken using PubMed. The search was performed using the search terms osteomyelitis, pediatric, bone infection, joint infection, hematogenous, sickle cell disease, imaging, and antibiotics. Additional papers were identified through bibliographies of key studies. Over 100 articles were reviewed. Searching the Cochrane Database of Systematic Reviews using the key term osteomyelitis identified 1 relevant review.¹⁴ The authors of this review attempted to determine whether an empiric antibiotic treatment approach was effective and safe compared to pathogen-directed treatment in this group of patients. The authors, were, however, unable to locate any trials on efficacy and safety, and we recommend that a randomized controlled trial should be undertaken to establish optimum antibiotic treatment. The Infectious Diseases Society of America has not published any clinical guidelines specifically for osteomyelitis; however, there is a guideline on treating prosthetic joint infections complicated by osteomyelitis.¹⁵ The Infectious Diseases Society of America is currently developing a new practice guideline on vertebral osteomyelitis, which is projected to be published in the spring of 2014. The American Academy of Pediatrics has not published any guidelines for the diagnosis or treatment of osteomyelitis in children.

The most notable study relevant to an emergency clinician’s perspective is the 2008 study by Riise et al.⁶ This multicenter prospective trial followed 429 children and investigated important questions related to incidence, laboratory values, imaging, and other diagnoses for children referred to the hospital with suspected osteomyelitis. This study found that the incidence of osteomyelitis was highest in patients aged < 3 years, erythrocyte sedimentation rate (ESR) ≥ 40 mm/h was the laboratory marker with the highest positive predictive value, magnetic resonance imaging (MRI) had a positive predictive value of 85%, and blood culture was only positive in 26% of patients with AHO. One comprehensive systematic review published in 2012 is a metaanalysis that included 132 articles incorporating more than 12,000 pediatric patients.¹ This review yielded comprehensive information on symptoms, location, laboratory markers, imaging, etiology, and treatment. Forty percent of children were afebrile on presentation, the femur and tibia are the most commonly infected bones, S aureus is the most common pathogen detected, and ESR is the most common abnormal laboratory value in children with AHO. Other than this systematic review, the majority of clinical evidence for pediatric AHO falls into Classes III and IV, based on the National Institutes of Health classifications, as osteomyelitis is rare and often difficult to study. When available, recommendations in this issue are evidence-based. Accepted practice and expert consensus are explicitly noted.

Risk Management Pitfalls For Acute Hematogenous Osteomyelitis

1. “The x-ray was normal, so I did not pursue a diagnosis of osteomyelitis.” X-rays are often normal in AHO, and non-specific changes are seen in only 15% to 58% of patients with AHO.^1,2,30,45 X-rays have even less sensitivity in pelvic osteomyelitis. It typically takes ≥ 7 days for changes associated with osteomyelitis to be seen on x-ray.^3,16,46
2. “The WBC count and differential were unremarkable, so it couldn’t have been osteomyelitis.” WBC count is the least helpful of the inflammatory markers, with a sensitivity of 34% to 43% in AHO.^1,29,31,41 ESR and CRP are most useful, and are elevated in 73% to 100% and 70% to 100% of patients, respectively.^{1,16,28,29,30,32,33,41}
3. “I treated a 6-month-old who had no MRSA risk factors with nafcillin and heard that his condition worsened the next day.” Although S aureus is the most common cause of AHO, there are certain populations where gram-negative bacilli coverage is also indicated or should be considered. This includes children aged < 5 years, children who have not completed the Hib vaccine series, and children with sickle cell disease.
4. “A young boy with abdominal pain, who had a negative CT scan 3 days ago, was discharged, and then returned to the ED and was diagnosed with pelvic osteomyelitis.” Pelvic osteomyelitis may present as hip, thigh, or abdominal pain, which frequently leads to delayed diagnosis and misdiagnosis. Keep pelvic osteomyelitis on your differential for any patient presenting with abdominal pain, as a misdiagnosis of pelvic osteomyelitis has been shown to cause significant permanent disability.
5. “An adolescent patient who had a renal transplant 1 year ago presented with pain over her femur. Her blood work was completely normal, so I discharged her. When she came back to the ED, I found I had missed osteomyelitis.” Immunosuppressed patients are at risk for less common etiologies of osteomyelitis, such as fungal osteomyelitis. It is important to remember that markers of systemic inflammation are often normal in fungal osteomyelitis.
6. “I suspected osteomyelitis, but the CRP was normal, so I decided AHO was ruled out.” No marker of inflammation, including CRP, is 100% sensitive for AHO. Clinical suspicion should prompt further testing even if all blood work is normal.
7. “A patient presented with findings of cellulitis. I did not do any blood work and treated with cephalexin. The symptoms returned after the antibiotic course was finished, and an MRI showed osteomyelitis.” Osteomyelitis can present with an overlying cellulitis with or without an abscess. These conditions can often be difficult to differentiate from one another. If there is any suspicion for deeper infection of the muscle or bone, emergency clinicians should get an initial plain radiograph and send a blood sample for measurement of CRP, ESR, and a WBC count with differential. Also consider obtaining CPK levels to rule out muscle involvement.
8. “A pediatric patient had a history of trauma at the site of leg pain, but the x-ray was negative. I sent him home with recommendations for ice, rest, and anti-inflammatory medicines. He returned later with worsening symptoms and was diagnosed with osteomyelitis.” A significant proportion of children with AHO have a history of trauma at the site of infection. Trauma to bone tissue may predispose it to hematogenous infection. A history of trauma should not deter emergency clinicians from further workup for osteomyelitis.
9. “My facility does not have MRI capability, so I referred a child with suspected osteomyelitis to a larger academic center.” Bone scan, ultrasound, or CT can aid in workup for osteomyelitis when MRI is not available. In most cases, clinical suspicion and a positive bone scan is sufficient evidence to support obtaining a bone sample for culture and to effectively treat AHO.
10. “I diagnosed osteomyelitis, recovered a microbe in blood and bone culture, and treated it with an effective antibiotic for 6 weeks. The patient returned several weeks after completion of the antibiotics with recurrence at the same site.” Treatment failure is common in osteomyelitis, occurring in 4.7% of children in 1 study.⁷¹ Even in the absence of sequestra or abscess, appropriate treatment can fail for reasons that are poorly understood.

Tables and Figures

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study, will be included in bold type following the reference, where available. In addition, the most informative references cited in this paper, as determined by the authors, will be noted by an asterisk (*) next to the number of the reference.

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6. * Riise OR, Kirkhus E, Handeland KS, et al. Childhood osteomyelitis- incidence and differentiation from other acute onset musculoskeletal features in a population-based study. BMC Pediatr. 2008;8:45. (Prospective multicenter; 429 patients)
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51. Mazur JM, Ross G, Cummings J, et al. Usefulness of magnetic resonance imaging for the diagnosis of acute musculoskeletal infections in children. J Pediatr Orthop. 1995;15(2):144- 147. (Prospective; 43 patients)
52. Pääkkönen M, Peltola H. Bone and joint infections. Pediatr Clin North Am. 2013;60(2):425-436. (Review article)
53. Guillerman RP. Osteomyelitis and beyond. Pediatr Radiol. 2013;43Suppl 1:S193-S203. (Review article)
54. Chamroonrat W, Zhuang H. Early acute hematogenous osteomyelitis detected by bone scintigraphy but not MRI. Clin Nucl Med. 2013;38(4):285-288. (Case report; 1 patient)
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63. Peltola H, Unkila-Kallio L, Kallio MJ. Simplified treatment of acute staphylococcal osteomyelitis of childhood. The Finnish Study Group. Pediatrics. 1997;99(6):846-850. (Prospective randomized; 50 patients)
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65. Bachur R, Pagon Z. Success of short-course parenteral antibiotic therapy for acute osteomyelitis of childhood. Clin Pediatr (Phila). 2007;46(1):30-35. (Retrospective; 29 patients)
66. Ceroni D, Regusci M, Pazos JM, et al. Risks and complications of prolonged parenteral antibiotic treatment in children with acute osteoarticular infections. Acta Orthop Belg. 2003;69(5):400-404. (Retrospective; 60 patients)
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68. Breda L, de Michele G, Nozzi M, et al. Non-tuberculous mycobacterial osteomyelitis: an unusual cause of hip pain in immunocompetent children. Rheumatol Int. 2009;29(12):1487- 1489. (Case report; 1 patient)
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