IntroductionSubacute osteomyelitis is a distinct form of
osteomyelitis, and Brodie abscess is one type of subacute
osteomyelitis. Subacute osteomyelitis is difficult to diagnose
because the characteristic signs and symptoms of the acute form of
the disease are absent.1,2,3 The disease has an insidious onset,
mild symptoms, and lacks a systemic reaction, and supportive
laboratory data are inconsistent. Subacute osteomyelitis may mimic
various benign and malignant conditions, resulting in delayed
diagnosis and treatment. The most frequently made incorrect
diagnosis is that of tumor.1,4,5 In noncontemporary literature,
Brodie abscess was referred to as a chronic form of osteomyelitis;
however, in almost all contemporary literature references, Brodie
abscess is referred to as the most common type of the subacute form
of osteomyelitis. For excellent patient education resources, visit
eMedicine's Cancer and Tumors Center and Cancer Screening Center.
Also, see eMedicine's patient education articles Bone Marrow Biopsy
and Cancer: What You Need to Know.
History of the ProcedureSir Benjamin Brodie, a surgeon in St.
George's Hospital, London, United Kingdom, first described subacute
osteomyelitis in 1832.6 He amputated the leg of a man who had
intractable pain for a number of years. On examination of the
amputated limb, Brodie found a cavity the size of a walnut filled
with dark-colored pus. The bone immediately surrounding the cavity
was whiter and harder than the surrounding bone. The inner surface
of the cavity appeared to be highly vascular.6 Since then,
low-grade pyogenic abscesses of the bone have frequently been
referred to as Brodie abscesses. In 1951, Wiles referred to Brodie
abscesses as a particular form of chronic osteomyelitis that
follows an acute attack, when the virulence of the organism and the
resistance of the patient are evenly balanced.7 Little discussion
exists in the literature again until Harris and Kirkaldy-Willis
described primary subacute osteomyelitis8 ; they were the first to
publish a radiograph that demonstrated an abscess of subacute
osteomyelitis crossing the epiphyseal plate of the distal tibia.
Based on their experience in East Africa, Harris and
Kirkaldy-Willis classified primary subacute osteomyelitis, into 2
types, depending on whether a bone abscess is present or not, with
the first type being metaphyseal and the second type diaphyseal.
Subsequently in 1973, Gledhill proposed a radiologic classification
for primary subacute osteomyelitis that consisted of 4 types based
on his review of 8 patients, as follows9 :
Type I Solitary lesion with surrounding sclerosis, classic
Brodie abscess Type II Metaphyseal radiolucent lesion with an
associated loss of cortical bone Type III Diaphyseal cortical
hyperostosis without onion-skinning Type IV Diaphyseal lesions
associated with onionskin layering
In 1982, Roberts et al modified and expanded Gledhill's
classification to 6 forms based on morphology, location, and
similarity to neoplasms, as follows10 (see image below):
Modified classification of subacute osteomyelitis. Type I is
metaphyseal. Type Ia is a punched-out central metaphyseal lesion.
Type Ib is an eccentric metaphyseal cortical erosion. Type II is
diaphyseal. Type IIa is a localized cortical and periosteal
reaction. Type IIb is a medullary abscess in the diaphysis without
cortical destruction but with onionskin periosteal reaction. Type
III is epiphyseal. Type IIIa is a primary epiphyseal osteomyelitis.
Type IIIb is a lesion that crosses the epiphysis and involves both
the epiphysis and the metaphysis. Type IV is a metaphyseal
equivalent. Type IVa involves the vertebral body with an erosive or
destructive process. Type IVb involves the flat bones of the
pelvis. Type IVc involves the small bones, such as the tarsal
bones.
Type Ia lesions present as a punched-out radiolucency that is
often suggestive of eosinophilic granuloma (see images below). Type
Ib lesions are similar to type Ia lesions but have a sclerotic
margin and appear as a classic Brodie abscess.
o
Anteroposterior radiograph of the distal radius. This image
depicts a central metaphyseal lesion (punched-out radiolucency),
type Ia.
o
Lateral radiograph of the distal radius. This image depicts a
central metaphyseal lesion (punched-out radiolucency), type Ia.
Type II lesions erode the metaphyseal cortex and may appear
similar to osteogenic sarcoma (see images below).
o
Anteroposterior radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
o
Lateral radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
Type III lesions are observed as a localized diaphyseal cortical
and periosteal reaction simulating osteoid osteoma (see images
below).
o
Anteroposterior and lateral radiographs of the distal femur.
These images depict a type IIIa epiphyseal lesion.
o
Lateral radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
o
Anteroposterior radiograph of the distal tibia. This image
depicts an eccentrically located radiolucent lesion crossing the
epiphyseal plate, type IIIb.
o
Lateral radiograph of the distal tibia. This image depicts an
eccentrically located radiolucent lesion crossing the epiphyseal
plate, type IIIb.
Type IV diaphyseal lesions most often resemble Ewing sarcoma,
with onionskin periosteal reaction (see images below).
o
Lateral radiograph of the lumbosacral spine. This image depicts
destruction of bone and disc space, type IVa.
o
Computed tomography scan cut of the right lower extremity. This
image depicts a sclerotic lesion of the right iliac bone, type
IVb.
Type V lesions occur in the epiphysis and appear as a concentric
radiolucency. Type VI lesions involve the vertebral body with an
erosive or destructive process.
This classification system is the most widely used in the
literature, and several reports advocate modifying the
classification system to include flat bone involvement, tarsal
bones, and lesions affecting both the metaphysis and the epiphysis.
Some authors have modified the Roberts's classification system (see
Introduction, Clinical, below). In all reported series of primary
subacute osteomyelitis, the classic Brodie abscess (central
metaphyseal lesion with well-defined sclerotic margins, type Ia
according to the authors' new classification system) has comprised
the largest number of cases.
ProblemSubacute osteomyelitis is characterized by mild to
moderate pain, usually described as a persistent ache; intermittent
symptoms; insidious onset; and, often, a long delay between the
onset of pain (the most common presenting symptom) and the
diagnosis. Usually, symptoms are present for 2 weeks or longer. The
course is generally marked by few or no constitutional symptoms and
no known previous acute disease.
FrequencyThe incidence of subacute osteomyelitis has increased
since antibiotics have been used to treat osteomyelitis. The
disease reportedly accounts for 8.8%,11 35%,12 and 42%13 of primary
bone infections, although a report by Blyth et al indicates a mild
decline in the incidence of both acute and subacute osteomyelitis,
with greater decline in the acute form than in the subacute form.14
In East Africa, subacute osteomyelitis is the most common form of
osteomyelitis. Onset of subacute osteomyelitis tends to occur in
slightly older children than the onset of acute osteomyelitis.
Subacute osteomyelitis has been reported in patients as young as 6
months and as old as 39 years, but the common age range is 2-15
years. Sex ratios vary, but in general, males are affected slightly
more often than are females.
EtiologySubacute osteomyelitis is one of the many clinical
presentations of hematogenous osteomyelitis. The organisms reach
the bone from a disrupted site elsewhere in the body that may pose
little or no threat of its own accord (eg, skin pustule, furuncles,
impetigo, infected blisters and burns). Infection has even been
suggested to be the outcome of common events such as normally
harmless daily teeth brushing. Factors that may influence the
behavior of a septic process in bone may relate to host resistance,
virulence of the infecting organism, and adequacy of antibiotic
therapy. Moreover, subacute osteomyelitis appears to depend on the
interplay between the infecting bacteria and the immune mechanism
of the host. True primary subacute osteomyelitis represents a
favorable host-pathogen response. In East Africa, where subacute
osteomyelitis is the most common form of osteomyelitis, children in
bare feet have frequent foot infections and develop a high
resistance to staphylococcal infections (the most common causative
organism), as pointed out by Harris and Kirkaldy-Willis.8 That
trauma results in vascular injury and an area of hypoxia in the
metaphyseal region of bone is an attractive theory, but it is
difficult to prove as an inciting cause of subacute osteomyelitis.
When
the host resistance is insufficient to overwhelm the infection,
it is conceivable that subacute osteomyelitis may develop. The
pyogenic organisms' initial attack is presumed to be controlled by
the host, and presumably, spread to large areas of cancellous
tissue or to the subperiosteal region has not occurred. A central
area of suppurative necrosis in the metaphyseal region becomes
enclosed by a wall of fibrous tissue and granulations, the
offending organisms are destroyed, and the pus is usually sterile.
The circulation of the epiphysis predisposes to sluggish blood flow
through the vascular loops. Possibly, the rich supply of the
reticuloendothelial cells located in the epiphysis attenuates the
osteomyelitis, leading to the subacute course in this region. The
metaphyseal-equivalent regions are defined as the portion of a flat
or irregular bone that borders cartilage (apophyseal growth plates,
articular cartilage, or fibrocartilage), such as the pelvis, the
vertebrae, the clavicle, and the small bones (tarsal bones).15 The
vascular anatomy and the mechanism of seeding are analogous to
those found in the metaphysis of long bones.
PathophysiologySite of infection Subacute osteomyelitis occurs
in a much wider variety of bones than does the acute type, and the
disease occurs at various sites within the affected bones. The
lower limb is affected much more often than the upper limb, and the
tibia is affected relatively more often than is the femur. Subacute
osteomyelitis may involve only the epiphysis, which is contrary to
the belief that primary bone infection does not occur in the
epiphysis (see image below).
Anteroposterior and lateral radiographs of the distal femur.
These images depict a type IIIa epiphyseal lesion.
The diaphysis is occasionally affected (see first 2 images
below), although this occurs more often in adults than in children;
the most commonly affected site is the metaphysis (see last 2
images below).
Anteroposterior radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
Lateral radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
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 image depicts a
central metaphyseal lesion (punched-out radiolucency), type Ia.
Communication of the lesion between the metaphysis and the
epiphysis is also common (see images below).
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 depicts an
eccentrically located radiolucent lesion crossing the epiphyseal
plate, type IIIb.
Other sites in which subacute osteomyelitis is frequently
reported are metaphyseal-equivalent locations, such as the pelvis,
the vertebrae, the calcaneum, the clavicle, and the talus. When
subacute osteomyelitis occurs in tarsal bones, it usually occurs in
the subchondral part or on the
border of the apophysis of the calcaneus. Subacute lesions of
the spine occur more often in adults than in children (see image
below).
Lateral radiograph of the lumbosacral spine. This image depicts
destruction of bone and disc space, type IVa.
When subacute osteomyelitis occurs in the long bones of adults,
the diaphysis is involved as often as is the metaphysis. The
patella is rarely involved. Multifocal subacute osteomyelitis is a
rare form of subacute osteomyelitis that was reported by Season and
Miller and by Rasool.16,17 It is usually associated with a
deficient immune system. Bacteriology The causative organism is
usually coagulase-positive Staphylococcus (30-60%). Other organisms
encountered are Streptococcus, Pseudomonas, Haemophilus influenzae
(much less common after widespread vaccination), and
coagulase-negative Staphylococcus. An increased prevalence of
Kingella kingae, a gram-negative coccobacillus, was noted by Lundy
and Kehl, mostly in children younger than 3 years as a cause of all
types of osteoarticular infections, including subacute
osteomyelitis.18 Patients with sickle cell anemia are predisposed
to infections with Salmonella, whereas Pseudomonas aeruginosa is
isolated from skeletally mature intravenous drug abusers. However,
in almost 25-50% of cases of subacute osteomyelitis, no organism is
cultured.
PresentationPresenting symptoms of subacute osteomyelitis
include mild to moderate localized pain. Pain is the most
consistent complaint in most patients, and it may at times become
more intense or remit and is frequently exacerbated following a
period of unusual activity. Night pain that is relieved with
aspirin is frequently reported. Minimal loss of function is another
common symptom (eg, limping in a patient with a lower limb lesion),
with no history of systemic toxicity. On clinical examination,
localized tenderness may only occasionally be associated with
warmth, redness, and soft-tissue swelling with the involvement of
subcutaneous bone. This finding seems to increase and subside with
activity. Pain may occur with movement of the adjacent joint, and
some joint effusion may be present, but the pain and effusion are
usually mild. The surrounding muscles may occasionally demonstrate
some wasting. Classification Ross and Cole categorized these
lesions either as aggressive or as cavities in the area of the
metaphysis and epiphysis.19 This categorization helps in the
treatment plan, as aggressive lesions
should be treated surgically for diagnosis. Gledhill classified
subacute osteomyelitis according to radiologic appearance,9 and
this classification scheme has since been modified by Roberts et
al.10 The classification scheme is useful for reporting the results
of treatment according to the site but is not a prognosis or
treatment plan. The authors have modified the latter as follows
(see image below):
Modified classification of subacute osteomyelitis. Type I is
metaphyseal. Type Ia is a punched-out central metaphyseal lesion.
Type Ib is an eccentric metaphyseal cortical erosion. Type II is
diaphyseal. Type IIa is a localized cortical and periosteal
reaction. Type IIb is a medullary abscess in the diaphysis without
cortical destruction but with onionskin periosteal reaction. Type
III is epiphyseal. Type IIIa is a primary epiphyseal osteomyelitis.
Type IIIb is a lesion that crosses the epiphysis and involves both
the epiphysis and the metaphysis. Type IV is a metaphyseal
equivalent. Type IVa involves the vertebral body with an erosive or
destructive process. Type IVb involves the flat bones of the
pelvis. Type IVc involves the small bones, such as the tarsal
bones.
Type I is a metaphyseal lesion. o Type Ia is a central
metaphyseal lesion that is seen as a punched-out radiolucency,
often suggestive of Langerhans cell histiocytosis (see images
below).
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 image depicts a
central metaphyseal lesion (punched-out radiolucency), type Ia.
o
Type Ib is a metaphyseal lesion eccentrically located with
cortical erosion, which
may give the appearance of osteogenic sarcoma. Type II is a
diaphyseal lesion. o Type IIa is a localized cortical and
periosteal reaction that simulates osteoid
o
osteoma. A type IIb lesion is a medullary abscess in the
diaphysis without cortical destruction but with onionskin
periosteal reaction that resembles Ewing sarcoma (see image
below).
Anteroposterior radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
Type III is an epiphyseal lesion. o Type IIIa is a primary
epiphyseal osteomyelitis and appears as a concentric radiolucency.
This type is usually seen in children younger than 4-5 years (see
image below).
Anteroposterior and lateral radiographs of the distal femur.
These images depict a type IIIa epiphyseal lesion.
o
Type IIIb is a subacute infection that crosses the epiphysis and
involves both the epiphysis and metaphysis (see images below).
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 depicts an
eccentrically located radiolucent lesion crossing the epiphyseal
plate, type IIIb.
A type IV lesion is a metaphyseal-equivalent lesion, which is
defined as the portion of a flat or irregular bone that borders
cartilage (apophyseal growth plates, articular cartilage, or
fibrocartilage), such as the vertebrae, the pelvis, and small bones
(eg, tarsal bones and clavicle).15 o Type IVa involves the
vertebral body with an erosive or destructive process (see image
below).
Lateral radiograph of the lumbosacral spine. This image depicts
destruction of bone and disc space, type IVa.
o
Type IVb involves the flat bones of the pelvis and is mostly
sclerotic, with neither erosion nor destructive processes. Ezra et
al mentioned this type in 1993 and 1997 (see image below).20,21
Computed tomography scan cut of the right lower extremity. This
image depicts a sclerotic lesion of the right iliac bone, type
IVb.
o
Type IVc involves the small bones (eg, tarsal bones,
clavicle).
Duration of symptoms Because the symptoms of subacute
osteomyelitis are vague, an accurate diagnosis is usually delayed.
The bone lesion may also not be readily apparent on plain
radiographs for some time.
The average duration of symptoms before diagnosis is 1-6 months,
but symptoms may be present longer before the diagnosis.
Differential diagnosis Osteomyelitis is a known mimic of various
diseases, and subacute osteomyelitis is no exception, having all of
the presenting signs and symptoms of many bone tumors, both benign
and malignant. The variety of radiographic presentations of
subacute osteomyelitis has been emphasized by Gledhill.9 The
classic solitary lesion located in the metaphysis surrounded by
reactive new bone presents little difficulty in diagnosis. However,
extensive erosions of cortical bone, periosteal new bone formation,
or both may add a more ominous dimension. Patients with subacute
osteomyelitis may occasionally be initially diagnosed with Ewing
sarcoma or osteogenic sarcoma. From these observations, the
following lesions must be considered among the differential
diagnosis of subacute osteomyelitis:
When the lesion is diaphyseal and associated with an onionskin
periosteal reaction, it may be confused with Ewing sarcoma,
Langerhans cell histiocytosis, or, much less likely, osteogenic
sarcoma. When the lesion is epiphyseal, it may be confused with a
chondroblastoma, fungal osteomyelitis, or tuberculous
osteomyelitis, or with an aneurysmal bone cyst, pigmented
villonodular synovitis (PVNS) erosions, giant cell tumor, or gout,
depending upon the age of the patient. Metaphyseal eccentric
lesions may be confused with the more common nonossifying fibroma,
although, typically, the diagnosis of nonossifying fibroma is
easily made, as is the diagnosis of chondromyxoid fibroma. Brodie
abscesses, osteoid osteoma, and intracortical hemangioma should all
be included in the differential diagnosis of an intracortical bone
lesion.
IndicationsSubacute osteomyelitis treatment is controversial;
however, in patients with characteristic clinical and imaging
findings and laboratory results, treatment with antibiotics alone
may be undertaken without biopsy, at least in the pediatric age
group.3,19,21,22,23,24,25 In the literature, opinion differs as to
whether treatment should be surgical or medical for these classic
lesions. Failure of symptoms to resolve after an up to 6-week
course of antibiotics or worsening of the condition during
treatment should lead to reevaluation and a definite tissue and/or
bacteriologic diagnosis, followed by surgical treatment and
appropriate antibiotics. Other indications for surgery are
impending sinus formation or drainage into a synovial joint.
Clinical signs of subperiosteal pus or synovitis indicate that the
subacute infection has transformed into an acute component, and it
must be drained surgically.
Relevant AnatomyInterconnecting subacute osteomyelitis of the
epiphysis and metaphysis is readily explainable in infants younger
than 18 months, when one considers that vascular communication
between the epiphysis and metaphysis is present until age 18
months, as described by Trueta.26 Epiphyseal lesions may also occur
in older adolescents when the growth plate becomes attenuated and
fails to provide a barrier to epiphyseal infection. Another
interesting explanation for the localization of subacute
osteomyelitis adjacent to the growth plate cartilage is the finding
by Speers and Nade that S aureus has a certain affinity for physeal
cartilage.27
The transgression of the epiphyseal plate from osteomyelitis
foci has been well documented (see images below). A review of the
literature indicates that despite localized transgression of the
epiphyseal plate by subacute osteomyelitis, growth plate arrest,
stimulation, or development of transepiphyseal bony bars is
exceedingly rare.
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 depicts an
eccentrically located radiolucent lesion crossing the epiphyseal
plate, type IIIb.
ContraindicationsContraindications to medical treatment alone
for subacute osteomyelitis include the following:
Failure of symptoms to resolve after an up to 6-week course of
antibiotics or worsening of the condition during treatment
Aggressive lesions (indistinguishable from malignant bone tumors)
Impending sinus formation or drainage into a synovial joint
Clinical signs of subperiosteal pus or synovitis
No literature exists to support medical treatment in adults, as
subacute osteomyelitis mostly affects patients in the pediatric age
group. Until medical treatment in adults is described, surgical
treatment of subacute osteomyelitis is indicated. No true
contraindications to surgical intervention exist, as medical
treatment alone without biopsy or curettage is still controversial
in the literature.
WorkupLaboratory StudiesThe laboratory workup of subacute
osteomyelitis includes the following:
The white blood cell (WBC) count is usually within the reference
ranges 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.
Imaging StudiesRadiologic findings o 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 wk to fit the diagnosis).
Typically, a localized destructive lesion of bone is present, with
surrounding sclerosis in the metaphysis (see images below).
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 image depicts a
central metaphyseal lesion (punched-out radiolucency), type Ia.
o
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 first 2 images below), or the lesion may
affect the epiphysis alone, although the articular cartilage itself
is unaffected (see 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. This image
depicts an eccentrically located radiolucent lesion crossing the
epiphyseal plate, type IIIb.
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 distal femur.
These images depict a type IIIa epiphyseal lesion.
o
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.)11 (See images
below).
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 depicts an
eccentrically located radiolucent lesion crossing the epiphyseal
plate, demonstrating the serpentine sign.
o
In diaphyseal lesions, periosteal reaction may occur with a
single layer or it may be laminated with or without bony
destruction (see image below).
Anteroposterior radiograph of the left tibia. This image depicts
periosteal reaction of the diaphyseal cortex, type IIb.
o
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 image below). The principal feature that
helps to distinguish subacute osteomyelitis from tuberculosis is
sclerosis of the vertebral body with a variable degree of
destruction of bone and disc 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 image depicts
destruction of bone and disc space, type IVa.
Bone scanning o Findings on technetium (Tc) bone scans are often
positive (see 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. 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 3-phase bone scan is
performed.
Total body scan. This image shows increased radionuclide uptake
at the distal left tibia.
Bone scan of both distal legs and feet. This image depicts
increased radionuclide uptake at the distal left tibia.
o
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 (111
In)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. Insufficient
data exist regarding the specificity of the newer scintigraphic
agents, Tc-99m (99m Tc) hexamethylpropyleneamine oxime
(HMPAO)labeled leukocytes, and nonspecific polyclonal111 In-labeled
immunoglobulin G (IgG). Although Roddie et al reported the use
of99m Tc HMPAOWBCs in 20 patients with suspected osteomyelitis in
general, with a reported sensitivity of 100% and specificity of
93%,28 the use of polyclonal human IgG is not approved in the US
despite its use in some European countries. The advantages of
polyclonal human IgG include the fact that it has a simple
preparation procedure compared with that of111 Inlabeled WBCs,
eliminates the need for phlebotomy and laborious labeling methods,
and reduces the patient radiation dose. Infecton (Draximage Inc,
Kirkland, Quebec, Canada) is another radiopharmaceutical, which is
based on ciprofloxacin that is labeled with99m Tc. 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 it is used in some hospitals in Europe. In
spinal infections, single photon emission (SPE) may reveal
abnormalities not
o
o
o
o
seen on the planar images. Degenerative disc disease is a cause
of false-positive bone scan results. Gallium specificity is greater
than 90% and is almost equivalent to magnetic resonance imaging
(MRI) for spinal infections. WBC scanning, however, is not
sensitive to vertebral osteomyelitis (40%). Computed tomography
(CT) scanning o Broaching of the physis may not always be apparent
on plain radiographs. It is more readily demonstrated by tomography
or by CT.
o
CT scanning is valuable in detecting lesions in difficult
anatomic locations that could not be seen with plain radiographs,
as in the pelvis and sacrum (see images below).
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. This image
depicts a round radiolucent lesion with a sclerotic margin.
o
CT scanning 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.
MRI
o o
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 first image below), whereas signal
intensity is increased on T2-weighted images (see second image
below), with a rim of decreased intensity due to sclerotic
bone.
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 ms, time
repetition = 2400 ms) magnetic resonance image through the distal
left tibial metaphysis. This image depicts a welldefined lesion of
increased signal intensity in the anterolateral aspect of the
distal left tibial metaphysis with a rim of decreased signal
intensity.
o
A gadolinium-enhanced image depicts a well-circumscribed
nonenhancing area with slight rim enhancement (see images
below.)
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 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.
o
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%
accuracy29 ; 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 MRIs (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. Gadolinium-based contrast agents
(gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine
[MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK],
and gadoteridol [ProHance]) have been linked to the development of
nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing
dermopathy (NFD). For more information, see the eMedicine topic
Nephrogenic Fibrosing Dermopathy. 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.
Diagnostic ProceduresFine needle aspirations (FNAs) of the
subacute osteomyelitis abscess cavity do not usually allow
isolation of the organism. Open drainage culture findings are
positive in 5075% 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.18 For this reason, K kingae or other similar
organisms may be the causative organisms associated with some cases
of so called culture-negative osteomyelitis.
Histologic FindingsIn 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
(PMLs), lymphocytes, and plasma cells are seen (see images below).
Pus under pressure is rarely encountered. The fluid content of the
cavity may be purulent, oily, or even mucoid.30 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 PMLs) between
the trabeculae of the medulla.
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 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 fibrosis, a
mixture of plasma cells, and occasional polymorphs. Hematoxylin,
phloxine, and safranin (HPS) X 25 X 1 X 5.
TreatmentMedical TherapyTreatment of subacute osteomyelitis
depends on the diagnosis. Almost one third of cases (the group that
was categorized by Ross and Cole as aggressive lesions19 ) are
indistinguishable from primary malignant bone tumors. Biopsy and
curettage are required for diagnosis in these cases. Once the
diagnosis is established, appropriate antibiotics (with the dose
adjusted according to the patient's weight and age) based on Gram
stain, culture, and sensitivity results should be initially started
intravenously for 2-7 days, followed generally by 6 weeks of oral
antibiotics. (Consultation with pediatric or adult infectious
diseases specialists is recommended for the appropriate antibiotic
dose, route, and duration.) Clinical and laboratory (ESR and CRP)
monitoring of clinical improvement is appropriate. Ezra et al
reported their criteria for changing from intravenous to oral
antibiotics to be marked cessation of pain, subsidence of swelling,
and functional improvement.20
In cases in which clinical and imaging findings and laboratory
results are characteristic (ie, the diagnosis is not uncertain),
although controversial, treatment with antibiotics alone may be
undertaken as suggested by Bogoch et al,22 Ross and Cole,19 Andrew
and Porter,23 Martin,25 Hamdy et al,24 Ezra et al,20,21 and
Gonzalez-Lopez et al.3 In the literature, opinion differs as to
whether treatment for these classic lesions should be surgical or
medical. Although most of the available pediatric orthopedic
literature supports medical treatment, no literature regarding
treatment in adults is available to support either medical or
surgical treatment (apart from recommending biopsy); most
orthopedic surgeons treating adults feel more comfortable with
surgical treatment. Ross and Cole reported an 87% success rate and
Ezra et al reported a 96% success rate with a single course of
medical treatment.19,20 Hoffman et al found that medical treatment
with only biopsy (no curettage) was successful in every case of
diaphyseal subacute osteomyelitis they treated (biopsy was required
to exclude malignancy).31 In another study, Ezra et al reported a
90% success rate in medically treating subacute osteomyelitis in
tarsal bones.21 Failure of resolution of symptoms after a course of
antibiotics of up to 6 weeks or worsening of the condition during
treatment should lead to reevaluation and a definite tissue
diagnosis, bacteriologic diagnosis, or both, followed by surgical
treatment and appropriate antibiotics. Other indications for
surgery are impending sinus formation or drainage into a synovial
joint. Clinical signs of subperiosteal pus or synovitis indicate
that the subacute infection has transformed into an acute
component, and it must be drained surgically. If treating
empirically, use a broadspectrum antibiotic that covers S aureus
first and other pathogens secondarily. Coverage should be
considered for H influenzae in young children who have not been
immunized adequately. Antibiotics administered orally for
osteomyelitis must be given in doses that often are 2-3 times that
of those recommended in the agents' package inserts. Patient (or
parent) education is essential to maintain the compliance that is
required for successful treatment. Absorption of the antibiotic to
produce effective concentrations at the site of infection is
documented by measuring the concentration of the antibiotic or the
antibacterial activity in serum.
Surgical TherapyIn case of the aggressive subacute osteomyelitis
lesion which is indistinguishable from a tumor, open biopsy for
culture and histology is indicated. Other lesions are incised and
drained when indicated, the granulation tissue present in the
lesion is curetted and cultured, and antibiotics are started
immediately after biopsy. In pediatric patients with typical
cavities in the metaphysis, the epiphysis, or in both, surgery is
undertaken only for specific indications. When clinical signs of
subperiosteal pus are present, incision and drainage is performed.
When clinical signs of synovitis are present, with a possibility of
pus within a joint, arthrotomy is performed and synovium is sent
for culture and histology studies. If metaphyseal or epiphyseal
cavities communicate with the joint they are curetted. Curettage of
cavities is also indicated if the symptoms and signs of infection
persist during conservative treatment or if they recur. Curettage
of metaphyseal cavities should be carried out carefully, and
perforations in the growth plate should not be curetted, because
curettage of the metaphyseal lesion usually decompresses the
epiphyseal lesion. Ross and Cole reported all epiphyseal cavities
in their study healed with a single course of antibiotics and
immobilization without operation.19 However, when drainage was
indicated, the procedure was not performed through the growth
plate. Green et al described curetting epiphyseal lesions after
localization by inserting a needle into the epiphysis and obtaining
2 plane
radiographs, then making a 2- to 3-mm drill hole to avoid the
weight-bearing or the articulating portion of the epiphysis.32 In
the proximal femoral epiphysis, the drill hole has to be
intracapsular as far distally as possible to avoid the portion of
the femoral head that articulates with the acetabulum while
avoiding the growth plate. In the distal femoral epiphysis, the
drill hole also has to be intraarticular but avoid the
weight-bearing articular surface coming medially or laterally.
Diaphyseal lesions may be difficult to treat surgically. In
patients with these lesions, the clinical picture is more likely to
resemble a tumor, and a surgical biopsy is necessary for diagnosis,
which should include adequate periosteum, cortical bone, and
medullary tissue. These usually respond to adequate antibiotic
therapy. In those cases with inadequate response to medical
treatment, exposure of the whole length of the affected bone is
indicated, with excision or exposure of all abscess cavities to
remove dead bone. The wound is sutured primarily and antibiotics
started.
Intraoperative DetailsIf surgery is undertaken for subacute
osteomyelitis lesions that measure more than 3 cm or in cases in
which bone is weak and subject to fracture, the cavity could be
filled with bone graft or bone graft substitutes (either primary
bone grafting,33 if the surgeon was happy about the total excision
of the abscess cavity to eliminate the dead space, or, more
appropriately, delaying bone grafting until the antibiotic
treatment is completed and the infection is believed to have been
eradicated based on clinical and laboratory results). Other options
include the temporary use of antibiotic cement beads and the use of
other alternatives to autologous bone graft, such as
antibiotic-laden bone graft substitutes. A drain is generally
indicated to avoid hematoma or seroma accumulation, which can lead
to recurrent abscess.
Postoperative DetailsIn epiphyseal lesions especially,
protection of the joints, either with traction or with splinting,
and starting protected motion early is a consideration (with
intermittent removal of the splint or traction for early range-of-
motion exercises). Due to the proximity of the cavity to the
articular surface and the risk of collapse, limitation of weight
bearing is indicated until evidence of partial healing of the
defect is seen on radiographs.
Follow-upFollow-up in cases of subacute of osteomyelitis should
continue for at least 2 years. In the first week, closely monitor
for signs of response to treatment (clinical and laboratory).
Monitor for compliance with antibiotic therapy for 6 weeks.
Clinical response is usually within a few days of initiation of
treatment. In the first 6 months, monitor for signs of recurrence.
Most recurrences occur within 6 months, but recurrence after up to
18 months has been reported. Radiologic healing is slower than
clinical healing and usually occurs within 3-12 months. Metaphyseal
and epiphyseal cavities usually disappear or heal, leaving either a
small area of sclerosis or a small, indistinct lucency in the
cortex. The purpose of follow-up after a year is mainly for
assessment of bone growth and alignment, although physeal growth is
very rarely affected.
ComplicationsIn pediatric cases of subacute osteomyelitis, 24%
of infants younger than 1 year experience complications, compared
with 8.5% of older children.13 In epiphyseal or
epiphyseal-metaphyseal lesions, due to the proximity of the cavity
to the articular surface, risk of collapse exists, as does
risk of pus discharge into the joint; Ross and Cole reported 2
such cases, one of the hip and one of the ankle joint.19 Effusions
into the hip joint were also reported by Ross and Cole in 2
patients who had closed cavities in the femoral neck.19 Injury to
the growth plate during surgical (curettage) treatment is also a
possibility. In large lesions, especially the diaphyseal lesions,
the involved bone might become weak and prone to fracture after
surgical treatment. Ross and Cole reported recurrence in 3 of 32
patients.19 Ezra et al reported recurrence in 1 of 21 patients
treated with antibiotics only20 ; all of their patients responded
to curettage and antibiotics. Stephens and MacAuley reported that
the age and sex of the patient, size of the abscess, and length of
intravenous therapy did not influence the rate of recurrence, but
they noted more recurrences in patients who were given a shorter
course of antibiotics (2-3 wk) and in patients with an initial high
ESR level (mean of 30 mm/h in the recurrence group compared with a
mean of 8 mm/h in the group without recurrences).33 Although
frequently located adjacent to the epiphyseal plate, subacute
osteomyelitis rarely results in retardation or stimulation of
growth, with Gonzalez-Lopez et al reporting a single case of 15-mm
growth stimulation (these lesions are quiescent lesions and
hyperemia is minimal)3 and Ross and Cole reporting a single case in
a child with a metaphyseal and epiphyseal lesion of the proximal
femur that resulted in growth retardation.19 Despite evidence of
penetration of the physis by the abscess, growth impairment is
extremely rare. Subacute abscesses that traverse the epiphyseal
plate do so in only one small cross-sectional area, which may
explain the absence of bony bridging. Growth disturbance, thus,
seems unlikely based on all the recorded experience with this
condition. That stated, Lindenbaum and Alexander reported a case
with varus recurvatum deformity of the knee (a
metaphyseal-epiphyseal lesion that was present for more than 3
years before treatment).5 Stephens and MacAuley reported coxa vara
in 1 patient, mild shortening (7 mm and 15 mm) in 2 patients, and
growth stimulation in 2 patients (7 mm and 10 mm).33
Outcome and PrognosisSubacute osteomyelitis is difficult to
diagnose, but, once diagnosed, it is a curable disease with a 100%
cure rate. Hamdy et al reported their results in treating 44
patients24 of which 24 were treated with antibiotics only, and 20
had surgical debridement followed by antibiotics. With the
exception of 1 patient who received inadequate antibiotic therapy,
all patients responded well, regardless of whether treatment was
conservative or surgical. At an average follow-up of 18 months, no
recurrences and no damage to the physis were reported.24 No good
outcome studies have been reported as of yet, but from the
available literature (apart from the previously mentioned rare
complications), the outcome of subacute osteomyelitis is excellent,
and full recovery is the rule in most cases.
Future and ControversiesSubacute osteomyelitis treatment remains
controversial. Some investigators agree that a conservative course
of antibiotic therapy is preferred. In lesions with an aggressive
character in which a tumor cannot be excluded, surgery is indicated
to establish the diagnosis. Diagnostic experience and awareness of
the condition significantly reduce the indications for surgery from
an approach in which biopsies are taken of all lesions, to an
approach in which biopsies are taken of only selected lesions.
Development of molecular assays for the direct detection of
microorganisms has been an actively growing specialty.
Amplification techniques such as those using polymerase chain
reaction (PCR) should provide increased sensitivity because of the
extensive amplification of target nucleic acid to identify the RNA
or DNA of viruses, bacteria, and other microorganisms in patients'
blood. At present, however, these techniques are not widely
available.