Subacute Osteomyelitis (Brodie Abscess) Workup

Updated: Aug 09, 2018
  • Author: Khalid I Khoshhal, MBBS, FRCS(Edin), ABOS; Chief Editor: Thomas M DeBerardino, MD  more...
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Workup

Laboratory Studies

The laboratory workup of subacute osteomyelitis includes the following:

  • The white blood cell (WBC) count is usually within the reference range or occasionally slightly elevated, with a normal differential
  • The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) measurements are usually mildly elevated, but they may be within the reference ranges in 30-50% of patients
  • Blood culture results are usually negative
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Radiography

The various radiologic techniques involved in the diagnosis of subacute osteomyelitis are important and complementary, rather than competitive. Radiologic osseous changes are often present, even in patients with a short history of symptoms (at least 2 weeks to fit the diagnosis). Typically, a localized destructive lesion of bone is present, with surrounding sclerosis in the metaphysis (see the images below).

Anteroposterior radiograph of the distal radius. T Anteroposterior radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia.
Lateral radiograph of the distal radius. This imag Lateral radiograph of the distal radius. This image depicts a central metaphyseal lesion (punched-out radiolucency), type Ia.

In some cases, a similar lesion with no surrounding sclerosis may be present. The lesion may cross the epiphyseal plate to affect the epiphysis as well (see the first and second images below), or the lesion may affect the epiphysis alone, though the articular cartilage itself is unaffected (see the third image below). Soft-tissue swelling overlying the lesion earlier in the course of the disease might be seen. A central bone density is occasionally seen in the presence of a sequestrum, which makes it difficult to differentiate subacute osteomyelitis from osteoid osteoma on plain films.

Anteroposterior radiograph of the distal tibia. Th Anteroposterior radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb.
Lateral radiograph of the distal tibia. This image Lateral radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, type IIIb.
Anteroposterior and lateral radiographs of the dis Anteroposterior and lateral radiographs of the distal femur. These images depict a type IIIa epiphyseal lesion.

On occasion, the lesion appears to become tethered to the growth plate, and the cavity progressively elongates, with growth extending from the epiphysis into the diaphysis in a snakelike fashion (the "serpentine sign" described by Letts). [23]  (See the images below.)

Anteroposterior radiograph of the distal tibia. Th Anteroposterior radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, demonstrating the serpentine sign.
Lateral radiograph of the distal tibia. This image Lateral radiograph of the distal tibia. This image depicts an eccentrically located radiolucent lesion crossing the epiphyseal plate, demonstrating the serpentine sign.

In diaphyseal lesions, periosteal reaction may occur with a single layer, or it may be laminated with or without bony destruction (see the image below).

Anteroposterior radiograph of the left tibia. This Anteroposterior radiograph of the left tibia. This image depicts periosteal reaction of the diaphyseal cortex, type IIb.

In spinal lesions (which occur more often in adults than in children), radiographs may show signs of healing by the time the diagnosis is made (see the image below). The principal feature that helps distinguish subacute osteomyelitis from tuberculosis is sclerosis of the vertebral body with a variable degree of destruction of bone and disk space, associated with relatively early new bone formation in the form of bony bridging between adjacent vertebral bodies. A paravertebral abscess may be present, but it is usually much smaller than in tuberculosis infections.

Lateral radiograph of the lumbosacral spine. This Lateral radiograph of the lumbosacral spine. This image depicts destruction of bone and disc space, type IVa.
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Nuclear Imaging

Findings on technetium (Tc) bone scans are often positive (see the images below), but false-negative results or, less likely, false-positive results are also possible. In addition, bone scan findings are nonspecific, simply demonstrating an increased vascularity or metabolic activity within the bone on the delayed image. 

Total body scan. This image shows increased radion Total body scan. This image shows increased radionuclide uptake at the distal left tibia.
Bone scan of both distal legs and feet. This image Bone scan of both distal legs and feet. This image depicts increased radionuclide uptake at the distal left tibia.

Close proximity of the focus of infection to the growth plate may render interpretation of bone scans difficult. The sensitivity and specificity of bone scanning have not been studied in subacute osteomyelitis, but they are better than 90% in cases of osteomyelitis of nonviolated bone when a three-phase bone scan is performed.

Because subacute osteomyelitis has such characteristic features on normal radiographic examination, bone scanning is seldom indicated unless the diagnosis is unclear and a bone scan is performed as part of a tumor workup. Also, bone scanning might be of help in delineating the rarely occurring multifocal subacute osteomyelitis.

Gallium scans and scans with indium 111 (111In)-labeled WBCs (WBC scan) have been used in conjunction with the Tc bone scan in the localization of infection, but they also remain nonspecific. Fractures and infarctions can lead to false-positive results with a WBC scan. In addition, these scans are more expensive, take longer to complete, and entail more radiation exposure (high absorbed radiation to the spleen and lymphocytes limit the injected dose in WBC scans) than Tc scans do.

There is a need for additional data on the specificity of the newer scintigraphic agents, Tc-99m (99mTc) hexamethylpropyleneamine oxime (HMPAO)-labeled leukocytes, and nonspecific polyclonal 111In-labeled immunoglobulin G (IgG). Roddie et al reported the use of 99mTc HMPAO-labeled WBCs in 20 patients with suspected osteomyelitis in general, with a reported sensitivity of 100% and specificity of 93%. [32]

The use of polyclonal human IgG for this application is not approved in the US, despite its availability in some European countries. Among the advantages of polyclonal human IgG are that it has a simple preparation procedure compared with that of 111In-labeled WBCs, that it eliminates the need for phlebotomy and laborious labeling methods, and that it reduces the patient radiation dose.

Infecton (Draximage, Kirkland, Quebec, Canada) is another radiopharmaceutical, which is based on ciprofloxacin that is labeled with 99mTc. The sensitivity is reduced for microorganisms with membranes impermeable to ciprofloxacin, but this method allows better differentiation between infection and sterile inflammation. Infecton is not available in the US but is used in some hospitals in Europe.

In spinal infections, single-photon emission (SPE) may reveal abnormalities not seen on the planar images. Degenerative disk disease is a cause of false-positive bone scan results. The specificity of gallium scanning is greater than 90% and is almost equivalent to that of magnetic resonance imaging (MRI) for spinal infections. WBC scanning, however, is not sensitive for vertebral osteomyelitis (40%).

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Computed Tomography

Broaching of the physis may not always be apparent on plain radiography. It is more readily demonstrated by tomography or by computed tomography (CT). CT is valuable in detecting lesions in difficult anatomic locations that could not be seen with plain radiography (eg, the pelvis and sacrum; see the images below).

Computed tomography scan cut of the right lower ex Computed tomography scan cut of the right lower extremity. This image depicts a sclerotic lesion of the right iliac bone, type IVb.
Computed tomography scan cut of the right sacrum. Computed tomography scan cut of the right sacrum. This image depicts a round radiolucent lesion with a sclerotic margin.

CT is also valuable in differentiating subacute osteomyelitis from osteoid osteoma. In osteoid osteoma, the nidus is central to the lesion, round, smooth, and well defined. In subacute osteomyelitis, a sequestrum, which is usually irregular and eccentric with respect to the radiolucent cavity, may occasionally be present.

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Magnetic Resonance Imaging

MRI is the most sensitive investigation in the evaluation of bone marrow pathology. Signal intensity is decreased on T1-weighted images of the lesion (see the first image below), whereas it is increased on T2-weighted images (see the second image below), with a rim of decreased intensity due to sclerotic bone.

Sagittal T1-weighted (time echo = 10 ms, time repe Sagittal T1-weighted (time echo = 10 ms, time repetition = 400 ms) magnetic resonance image of the left ankle. This image depicts a well-defined lesion of decreased signal intensity in the anterior aspect of the distal tibial metaphysis, which extends into the adjacent growth plate and epiphysis.
Axial fast spin echo T2-weighted (time echo = 48 m Axial fast spin echo T2-weighted (time echo = 48 ms, time repetition = 2400 ms) magnetic resonance image through the distal left tibial metaphysis. This image depicts a well-defined lesion of increased signal intensity in the anterolateral aspect of the distal left tibial metaphysis with a rim of decreased signal intensity.

A gadolinium-enhanced image depicts a well-circumscribed nonenhancing area with slight rim enhancement (see the images below.)

Sagittal postgadolinium-enhanced T1-weighted (time Sagittal postgadolinium-enhanced T1-weighted (time echo = 10 ms, time repetition = 650 ms) magnetic resonance image with fat saturation. This image shows a hypodense lesion centrally (fluid) with a moderately thick enhancement, which extends through the growth plate into the epiphysis.
Coronal postgadolinium-enhanced T1-weighted (time Coronal postgadolinium-enhanced T1-weighted (time echo = 10 ms, time repetition = 650 ms) magnetic resonance image with fat saturation. This image depicts a hypodense lesion centrally (fluid) with a moderately thick enhancement, which extends through the growth plate into the epiphysis.

A characteristic but not pathognomonic MRI finding that supports the diagnosis of subacute osteomyelitis and helps to exclude the presence of a tumor is the penumbra sign, which was reported by Grey et al to have 75% sensitivity, 99% specificity, and 99% accuracy [33] ; in their experience, the penumbra sign did not appear to occur with any great frequency in other osseous conditions.

The penumbra sign is characteristically seen on T1-weighted MRI (2- to 5-mm thickness) and is due to a thick layer of highly vascularized granulation tissue. (The presence of a layer of granulation tissue lining a cavity is important in the differentiation of an abscess from a tumor.) It is a discrete peripheral zone of marginally higher signal intensity than the abscess cavity and surrounding marrow edema/sclerosis and of lower signal intensity than the fatty bone marrow. The hyperintensity may be due to the high protein content of the granulation tissue. A similar appearance has been described in the wall of brain abscesses.

Contrast-related nephropathy

Gadolinium-based contrast agents (gadopentetate dimeglumine, gadobenate dimeglumine, gadodiamide, gadoversetamide, and gadoteridol) have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). NSF/NFD has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

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Procedures

Fine-needle aspiration (FNA) of the subacute osteomyelitis abscess cavity does not usually allow isolation of the organism. Open drainage culture findings are positive in 50-75% of patients. Whether the culture-negative abscesses are truly negative or whether they are caused by fastidious organisms remains to be investigated.

K kingae, for example, is a relatively new pathogen that has appeared to replace the predominance H influenzae in children younger than 3 years and is known to have a tenuous nature that can make it difficult to isolate on cultures. [17]  For this reason, K kingae or other similar organisms may be the causative organisms associated with some cases of so-called culture-negative osteomyelitis.

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Histologic Findings

In subacute osteomyelitis, the surrounding bone is usually sclerotic, but it is of variable thickness, most often thin rather than dense and thick. For most lesions, granulation tissue lines the abscess cavities, and the presence of fat, fibroblastic response (commonly, a fibrin layer separates bone from granulation tissue), remnant of necrotic bone, and new bone formation is seen.

Inflammatory infiltration in the form of acute and chronic cells consisting of polymorphonuclear lymphocytes (PMNs), lymphocytes, and plasma cells are seen (see the images below). Pus under pressure is rarely encountered. The fluid content of the cavity may be purulent, oily, or even mucoid. [34] In diaphyseal lesions at operation, thickened periosteum with a thickened hard cortex without pus is usually encountered. The histologic appearance is usually that of subperiosteal new bone formation with inflammatory cells (plasma cells, fibroblasts, and PMNs) between the trabeculae of the medulla.

Histologic section of bone. This image depicts sub Histologic section of bone. This image depicts subacute osteomyelitis with a mixture of polymorphs and plasma cells in an edematous background. Hematoxylin, phloxine, and safranin (HPS) X 440.
Histologic section of bone. This image shows fibro Histologic section of bone. This image shows fibrosis, degenerating bone spicules, and subacute inflammation. Hematoxylin, phloxine, and safranin (HPS) X 10 X 1 X 5.
Histologic section of bone. This image depicts fib Histologic section of bone. This image depicts fibrosis, a mixture of plasma cells, and occasional polymorphs. Hematoxylin, phloxine, and safranin (HPS) X 25 X 1 X 5.
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