Subacute Osteomyelitis

Key Points:

  • The most common causative organism is Staphylococcus aureus
  • In contrast to acute osteomyelitis, children with subacute osteomyelitis often lack systemic signs of infection.  Laboratory tests are often normal and blood cultures yield no organism. 
  • The diagnosis of subacute osteomyelitis should be considered in the limping child with focal tenderness, especially in the patient who has received antibiotics for an unrelated infection in the weeks prior.
  • Imaging studies may reveal an aggressive appearing lesion and malignancy must be ruled out. 
  • Whether treated with antibiotics alone or in combination with surgical debridement, outcomes of treated subacute osteomyelitis generally result in resolution of the symptoms and regression of the radiographic changes.

Description:

Subacute osteomyelitis, defined by King and Mayo as an osseous infection with a duration of more than two weeks without acute symptomatology, is a less common entity than acute hematogenous osteomyelitis.  It often presents with prolonged symptoms, typically bone pain and radiographic changes, without systemic signs or symptoms. (King, 1969) The lack of systemic illness, as opposed to acute osteomyelitis, can result in delayed diagnosis.  Subacute osteomyelitis may be the result of inadequate treatment for acute osteomyelitis or may occur in the setting of a more robust host resistance to infection, inoculation with less virulent organisms, prior antibiotic exposure or a combination of these factors. (Hamdy, 1996) Arriving at the correct diagnosis is often onerous and is delayed, on average, 3 to 5 months.  (Gonzalez-Lopez, 2001; Roberts, 1982; Herring, 2008) The medical evaluation is often more extensive due to the broader differential diagnosis.  The average age at diagnosis reported in the literature is between 7 and 9 years, with a range of 6 months to 16 years. (Roberts, 1982) This average age is greater than that of acute hematogenous osteomyelitis, which is 6.6 years. (Dartnell, 2012) While osteomyelitis may be diagnosed at any age and in any location, epiphyseal or apophyseal involvement is more common in children less than 4 years of age.  The average age reported by Ceroni et al for their series of patients with primary epiphyseal or apophyseal subacute osteomyelitis (PEASAO) was 27.8 months, which is compared to the average age of 46.4 months reported in their review of the current literature. (Ceroni, 2014) As children approach 18 months of age, the transphyseal vessels begin to involute, which hinders the spread of osteomyelitis to the epiphysis, allowing the physis to act as a natural barrier.  This is responsible for the predilection of metaphyseal involvement, however, epiphyseal and diasphyseal involvement is more frequently identified in subacute osteomyelitis as compared to acute hematogenous osteomyelitis.

Epidemiology:

Clinical Findings:

Unlike in the acute form, subacute osteomyelitis presents with the absence of fever or other constitutional symptoms, fatigue, malaise or anorexia, etc.  However, children will often have intermittent limp or pain at the site of infection.  On physical examination, the only finding is often tenderness with palpation at the involved site, which is most commonly in the lower extremity.  This picture is juxtaposed to that of a child with systemic signs including fever, acute onset of pain and diminished function of the afflicted limb in acute osteomyelitis.

Laboratory Evaluation
 
Inflammatory indices, blood cultures and complete blood count are often not helpful.  The serum white blood cell count (WBC) is typically normal to slightly elevated.  The erythrocyte sedimentation rate (ESR) is usually slightly elevated while the C-reactive protein (CRP) may be normal.  Blood cultures are routinely negative.  With advances in PCR assays, the ability to isolate a causative organism has improved.

Imaging Studies:

Plain radiographs are the initial imaging modality of choice.  X-rays may demonstrate a well circumscribed radiolucent lesion in the metaphysis, diaphysis, or epiphysis.  Additionally, plain radiographs may also demonstrate intense periosteal new bone formation that can be mistaken for a malignant process.  In contrast to chronic osteomyelitis, there is absence of both the sequestrum and involucrum.  Advanced imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and bone scan, can all provide useful information.   The currently utilized classification system was initially proposed by Gledhill in 1973 and then modified by Roberts et al in 1982.  There are six classification categories based on the anatomic location, presence or absence of an aggressive appearance, and the visualized host response. (Gledhill, 1973; Roberts, 1982)
 
Type IA: Metaphyseal radiolucency without surrounding sclerosis.  This group may be confused with an eosinophilic granuloma.
Type IB: Metaphyseal radiolucency with surrounding reactive bone.  This group includes the classic Brodie’s abscess.  
Type II: Metaphyseal radiolucency with cortical erosion.  This group may have the appearance of an osteosarcoma.
Type III: Cortical diaphyseal radiolucency with periosteal reaction.  This may resemble an osteoid osteoma.
Type IV: Diaphyseal lesion with subperiosteal new bone formation.  This group may have the appearance of “onion-skinning” and thus be confused with Ewing’s sarcoma.
Type V: Epiphyseal radiolucency that may appear similar to a chondroblastoma.
Type VI: Vertebral lesion that may mimic eosinophilic granuloma or tuberculous spondylitis

Etiology:

While the inciting pathway is similar for acute osteomyelitis and subacute osteomyelitis, the less virulent presentation of the subacute form may be due to several factors, including greater host resistance, less virulent organisms and/or recent antibiotic exposure.  Furthermore, inadequate antibiotic therapy for acute osteomyelitis may result in the genesis of subacute osteomyelitis.  Staph aureus remains the most commonly identified organism with Kingella kingae considered an important alternative pathogen to consider, especially in apparent culture negative cases in younger children. (Ceroni, 2014) In some facilities, it is routine to culture patients between the ages of 6 months and 5 years for Kingella kingae.  The sample must be sent for culture in blood culture bottles.  Strategies to improve identification of Kingella kingae include PCR assay to identify the RTX toxin, as even in an optimized conventional culture environment, successful isolation of K. kingae is not the rule. (Basmaci, 2012; Ceroni 2014) Other organisms implicated in subacute osteomyelitis include Salmonella, Strep species and Mycobacterium tuberculosis.

Treatment:

If imaging does not demonstrate features concerning for malignancy, empiric treatment with antimicrobials providing coverage for Staph aureus may be successful.  In children under 5 years of age antibiotic coverage should also include Kingella kingae.  Further consideration regarding the use of Clindamycin as empiric therapy is necessary, as 40% of K. kingae infections may be resistant. (Yagupsky, 2001) However, if concerning radiographic features are present, biopsy is mandated to rule out malignancy. (McCarthy, 2005) If biopsy and culture results confirm osteomyelitis, treatment should be undertaken.  In 1996, Hamdy et al published a review of 44 patients with subacute osteomyelitis treated with antibiotics alone, N = 24, or with a combination of surgical curettage/debridement and antibiotics, N = 20.  Both groups received 6 weeks of antibiotics and there was no difference in outcomes between the two groups.  Clinical response was noted within a few days of therapy initiation, while radiographic change took 3 to 12 months.  Further recommendations provided in this manuscript include reservation of surgical procedures for patients who do not experience clinical improvement after a trial of conservative care with antibiotics.  Moreover, they also support open biopsy in the setting of malignant features on initial imaging or for worsening radiographic findings after a trial of antibiotics. (Hamdy, 1996) 
 
While there are no current consensus guidelines, many authors prefer to obtain a biopsy of even benign appearing lesions for diagnostic purposes.  The biopsy should be sent for anatomic pathology and microbiology including aerobic, anaerobic, fungal, and AFB cultures.  If the diagnosis ultimately is a benign bone lesion, then the patient will avoid a prolonged exposure to antibiotic therapy.

Complications:

Subacute osteomyelitis, if not adequately treated, can progress to chronic osteomyelitis.  However, with appropriate and adequate treatment, the infection is usually eradicated and symptoms resolve.  In rare circumstances, growth disturbances may occur.  Ceroni et al did not identify any growth disturbances in their series, though follow-up duration was limited to an average of 34 months with 6 children having less than 2 years follow up. (Ceroni, 2014) Gonzalez-Lopez et al only identified one patient, out of 21, with a growth deformity, resulting in a 1.5-centimeter limb length difference due to growth stimulation (Gonzalez-Lopez, 2001). The risk of growth disturbance may be associated with aggressive curettage in the juxtaphyseal metaphysis.  While the literature lacks an aggregate rate of growth complications, the young physis appears to be resilient with rare reports of growth disturbance despite a substantial incidence of radiographic violation of the physis.

References:

  1. Basmaci R, Ilharrebirde B, Bidet P, Doit C, Lorrot M, Mazda K, Bingen E, Bonacorsi S. Isolation of Kingella kingae in the oropharynx during K. kingae arthritis in children. Clinical Microbiology and Infection. 2012 May;18(5):E134-136.
  2. Ceroni D, Belaieff W, Cherkaoui A, Lascombes P, Schrenzel J, de Coulon G, Dubois-Ferriere V, Dayer R. Primary Epiphyseal or Apophyseal Subacute Osteomyelitis in the Pediatric Population: A Report of Fourteen Cases and a Systematic Review of the Literature. J Bone Joint Surg Am. 2014;96:1570-5.
  3. Dartnell J, Ramachandran M, Katchburian M. Haematogenous Acute and Subacute Paediatric Osteomyelitis: A Systematic Review of the Literature. J Bone Joint Surg Br. 2012; 94-B:584-95.
  4. Gledhill RB. Subacute osteomyelitis in children. Clin Orthop Relat Res. 1973 Oct;(96):57-69.
  5. Gonzalez-Lopez JL, Soleto-Martin FJ, Cubillo-Martin A, et al.  Subacute osteomyelitis in children. J Pediatr Orthop B 2001;10: 101-4.
  6. Hamdy RC, Lawton L, Carey T, et al. Subacute hematogenous osteomyelitis: Are biopsy and surgery always indicated? J Pediatr Orthop 1996; 16:220-3.
  7. Herring JA. Tachdjian’s Pediatric Orthopaedics, 4th ed. Philadelphia: Elsevier, 2008:2089-2155.
  8. King DM, Mayo KM. Subacute haematogenous osteomyelitis. J Bone Joint Surg Br. 1969 Aug;51(3):458-63.
  9. McCarthy JJ, Dormans JP, Kozin SH, Pizzutillo PD: Musculoskeletal infections in children: Basic treatment principles and recent advancements. Instr Course Lect 2005;54:515-528.
  10. Roberts JM, Drummond DS, Breed AL, et al. Subacute hematogenous osteomyelitis in children: A retrospective study. J Pediatr Orthop 1982;2: 249-54.
  11. Yagupsky P, Katz O, Peled N. Antibiotic susceptibility of Kingella kingae isolates from respiratory carriers and patients with invasive infections. J Antimicrob Chemother. 2001;47(2):191–193.

Top Contributors:

Lindsay Stephenson MD
Howard Epps MD
Scott Rosenfeld MD