Hematogenous osteomyelitis in infants and Children: Imaging of a … · 2017-05-31 · ical manifestations and management, we must adjust the imaging approach to the disease. In this

Reviews and Com

mentaRy

n Review

Radiology: Volume 283: Number 3—June 2017 n radiology.rsna.org 629

1 From the Departments of Radiology (D.J., J.D.) and Pediatrics (J.W.S.G.), Children’s Hospital of Philadelphia, Philadelphia, Pa; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa (D.J., J.W.S.G.); Depart-ment of Pediatric Orthopaedic Surgery, Texas Children’s Hospital, Houston, Tex (J.P.D.); Department of Orthopedic Surgery, Baylor College of Medicine, Houston, Tex (J.P.D.); Department of Radiology and Medical Imaging, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (T.L.); and Department of Radiology, University of Cincinnati College of Medicine, Cincinnati, Ohio (T.L.). Received September 18, 2015; revision requested October 26; revision received April 19, 2016; accepted May 11; final version accepted June 3. Address correspondence to D.J., Department of Radiology, Miami Children’s Hospital, 3100 SW 62 Ave, Miami, FL 33155 (e-mail: [email protected]).

q RSNA, 2017

In children, hematogenous osteomyelitis is an infection that primarily affects the most vascularized regions of the growing skeleton. The disease has increased in frequency, virulence, and degree of soft-tissue involvement. The change in clinical manifestations and management over the past 2 decades should be reflected in the current imaging approach to the disease. Imaging of infection must depict the location of a single focus or of multiple foci of involvement and the presence of drainable collec-tions. This review provides an overview of the imaging implications directed by the changing epidemiology, the newer insights of anatomy and pathophysiology, the im-aging characteristics with emphasis on specific locations and disease complications, and the differential diagnosis considerations. In addition, basic imaging guidelines for appropriate extent of area to image based on patient age are provided.

q RSNA, 2017

Diego Jaramillo, MD, MPHJohn P. Dormans, MDJorge Delgado, MDTal Laor, MDJoseph W. St. Geme III, MD

Hematogenous osteomyelitis in infants and Children: Imaging of a Changing Disease1

Learning Objectives:

After reading the article and taking the test, the reader will be able to:n Identify the main questions in the management of osteomyelitis in children that can be answered with imagingn Describe the changes in imaging approach related to the changing epidemiology of acute hematogenous osteomyelitis in childrenn Discuss the relative merits of the different imaging modalities for the evaluation of osteomyelitis

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630 radiology.rsna.org n Radiology: Volume 283: Number 3—June 2017

REVIEW: Hematogenous Osteomyelitis in Infants and Children Jaramillo et al

tissue necrosis and destruction of neu-trophils (9), and is associated with a higher rate of septic shock and greater need for surgical interventions and pro-longed hospitalization (10). Children with PVL-positive staphylococcal infec-tions are more likely to have multifocal osteomyelitis, large subperiosteal ab-scesses, multiple bony abscesses, deep venous thrombosis, and associated myositis and pyomyositis (11).

In the past 10–15 years, there has been a remarkable increase in the rec-ognition of K kingae as an infecting organism. In Europe and the Middle East, K kingae now is the most com-mon pathogen in young children with osteomyelitis or septic arthritis (1). This bacterium is a facultative anaero-bic, b-hemolytic, gram-negative bacillus that colonizes the posterior pharynx of approximately 10% of healthy chil-dren between 12 and 24 months of age. Disease due to K kingae affects mostly children between 6 months and 4 years of age and involves primarily the mus-culoskeletal system in the form of sep-tic arthritis, spondylodiscitis, and oste-omyelitis. K kingae is difficult to recover from cultures, even when samples are inoculated into blood culture vials. It was largely unrecognized in the past, but polymerase chain reaction–based assays have been increasingly used for diagnosis, as this technique greatly en-hances the detection of the organism.

Osteomyelitis affects primarily young children, with half of all pedi-atric cases in children younger than 5 years of age (3). Children affected by K kingae are even younger, as the disease is almost always seen before the age of 4 years. Boys are affected twice as often as girls, and this difference has been ascribed to a greater exposure to microtrauma (1). The role of trauma

to be associated with complications. An important aspect of the disease involves the tissues outside the bone (Fig 1). As it has become clear that more prompt and better-targeted therapy leads to better outcomes, pharmacological and surgical therapies also have been mod-ified (1,2). Given the changes in clin-ical manifestations and management, we must adjust the imaging approach to the disease. In this review, we will emphasize the changing epidemiology and clinical manifestations of osteomy-elitis and discuss the implications for imaging.

Definition and Epidemiology

Acute hematogenous osteomyelitis is an infection that usually affects the grow-ing skeleton, involving primarily the most vascularized regions of the bone. It is considered an acute process if the symptoms have lasted less than 2 weeks (2,3). Acute osteomyelitis has an inci-dence of 8–10 per 100 000 in developed countries and an even higher incidence, up to 80 per 100 000, in developing countries (1,4,5). The incidence of sep-tic arthritis is about half that of oste-omyelitis. In the United States, there has been a 2.8-fold increase in the inci-dence of osteomyelitis in the past 2 de-cades (6). By contrast, over this same period, the incidence of septic arthritis has remained unchanged (7).

The most common organism that infects the bones is Staphylococcus au-reus, followed by the respiratory path-ogens Kingella kingae, Streptococcus pyogenes, and Streptococcus pneu-moniae (1,6,8). Both methicillin-sen-sitive and methicillin-resistant isolates of S aureus are associated with osteo-myelitis. Methicillin-resistant S aureus (MRSA) accounts for 30%–40% of osteoarticular infections in the United States and a lower percentage of cases in northern Europe and the Middle East (2). The course of community-acquired S aureus osteomyelitis appears to be more severe in recent years, primarily in cases caused by MRSA and potentially related to the presence of the Panton-Valentine leucocidin, or PVL, gene. This gene encodes for a toxin that produces

Published online10.1148/radiol.2017151929 Content codes:

Radiology 2017; 283:629–643

Abbreviations:MRSA = Methicillin-resistant Staphylococcus aureusSTIR = short-tau inversion recovery

Conflicts of interest are listed at the end of this article.

Essentials

n The bacteriology of pediatric os-teomyelitis has changed due to (a) increased virulence of Staph-ylococcus aureus, primarily of the methicillin-resistant strains, with more frequent subperiosteal abscess, soft-tissue involvement, multifocality, deep venous throm-bosis, and pathologic fractures and (b) increased incidence of Kingella kingae in younger children.

n K kingae results in a milder clin-ical presentation, is difficult to diagnose unless polymerase chain reaction is used, frequently involves the epiphyses and spine, and is less often associated with complications during treatment.

n The metaphysis is the primary site of infection in children owing to its abundant vascularity; a metaphyseal equivalent, at the junction of bone and cartilage in a skeletally immature flat or round bone, has similar vascu-larity to the metaphysis of a long bone, and therefore, is also par-ticularly susceptible to osteomyelitis.

n Imaging of pediatric osteomyelitis should answer: whether there is infection, what is its location, whether it is multifocal, whether there are drainable collections, and whether there are poor prognostic signs such as an extensive subperiosteal abscess or bone marrow ischemia.

n Changes in clinical presentation over the past few years mandate the need to image the tissues that surround the bone, and the adjacent joint and veins, by the use of either sonography or MR imaging.

T he clinical and radiologic pre-sentation of acute hematogenous osteomyelitis in children has

changed substantially over the past 2 decades. The disease is now more com-mon, more destructive, and more likely



highly vascularized, have sluggish flow, and contain more hematopoietic marrow than the remainder of the adjacent bone. These so-called metaphyseal equivalents (20) exist in the vicinity of the triradiate cartilage (Fig 4), the ischiopubic synchon-drosis, the sacroiliac joint, the periphery of round bones such as the talus, and the periphery of the secondary centers of ossification. In these bones, osteomyeli-tis begins in the metaphyseal equivalent locations. A targeted search for a focus of infection in the metaphyseal equiva-lents is particularly important in the pel-vis, where the infection of bone may be subtle relative to the more pronounced surrounding soft tissue changes (Fig 4b).

The periosteum of the growing skeleton has two layers: a superficial, strong layer called the fibrous perios-teum and an inner, very vascular layer called the cambium of the periosteum, which plays a role in membranous bone growth (21). An infection can reach the subperiosteal space, probably from the metaphyseal focus but possibly also by means of direct seeding (22), and subse-quently disseminate through the vascu-larized cambium (23). The fibrous layer of the periosteum can be separated easily from the underlying parent bone by pus, and a subperiosteal abscess can develop. The spread of a subperiosteal

metaphyseal spongiosa contains abun-dant blood vessels with leaky endothe-lium and sluggish flow that end in capil-lary loops (13). More recent research has found that these vessels actually are terminal and that bacteria lodge at the junction between the physis and the metaphysis (16). The periosteum also is highly vascular in the child, but it is unclear whether it can be the site of origin of infection (17).

In the first 18 months of life there is a communication between the epiphyseal and metaphyseal vessels (18). This com-munication results in direct extension of metaphyseal infections into the epiphysis (Fig 3). Epiphyseal extension can cause destruction of the epiphyseal cartilage and secondary ossification center and also can affect the cells of the germinal zone of the physis, which ultimately re-sult in permanent growth disturbance. Easy extension into the epiphysis also contributes to the higher incidence of septic arthritis in this age group (14). Transphyseal extension of pyogenic oste-omyelitis is considerably more common than is classically taught (19).

The junctions of bone and cartilage in skeletally immature flat bones, round bones, and epiphyseal ossification cen-ters have a structure similar to that of the metaphyses of long bones. They are

is important, as highlighted by the fact that one-third of children with osteomy-elitis have a history of a recent injury (12). Other organisms play a role in infections within specific populations. Gram-negative organisms such as Esch-erichia coli and group B streptococci are more common in neonates and young infants (13), and in one series accounted for 60% of musculoskeletal infections seen before 4 months of age (14). Pseudomonas aeruginosa infec-tion occurs in association with puncture wounds through sports shoes, and Sal-monella infection is prominent in pa-tients with sickle cell disease (4). Fun-gal osteomyelitis is most often due to Candida species and generally occurs in immunocompromised hosts. Similarly, mycobacterial osteomyelitis occurs in immunocompromised patients and among children living in regions where mycobacteria are endemic (14).

Pertinent Anatomic Concepts

The current paradigm describing the anatomic basis of osteomyelitis in chil-dren comes from the seminal work of Trueta (15), who established that the metaphysis is the primary site of in-fections (Fig 2) because of its vascu-lar characteristics. He found that the

Figure 1

Figure 1: Pattern of spread of infection. From the initial metaphyseal focus, the infection can spread into the epiphysis, the joint space, the subperiosteal space, the soft tissues, and the shaft of the bone.

Figure 2

Figure 2: Coronal fat-suppressed gadolinium-enhanced T1-weighted magnetic resonance (MR) image in a 14-year-old boy with fever and knee pain shows diffuse lateral metaphyseal enhancement with a small nonenhanced focus (arrow) adjacent to the physis.

Figure 3

Figure 3: Vascularity in the first 18 months of life. There is free communication between the vessels of the epiphysis and the metaphysis. Transphyseal vessels can serve as a path of spread of infection from one region to another, usually from metaphysis to epiphysis.



subperiosteal collection can lead to is-chemia of the bone (24,25).

Some metaphyses such as the prox-imal femur and the proximal radius are intracapsular. This anatomy allows an infection to spread directly from the affected metaphysis into the adjacent joint space. In other joints, such as the knee, the infection invades the joint only after it affects the epiphysis.

Diagnosis and Key Imaging Questions

Imaging must be tailored to answer those questions that will alter manage-ment. Osteomyelitis can be difficult to detect clinically as symptoms, physical examination, and laboratory findings can be deceptive at presentation, var-iable, and nonspecific (26). The main questions to be addressed by imaging are as follows: (a) Is there an infection? (b) Where is the infection? (c) Are there drainable collections?

Is There an Infection?We need to confirm or exclude acute os-teomyelitis. Prompt diagnosis is crucial for a successful outcome, since compli-cations of osteomyelitis increase mark-edly when treatment is delayed. A delay in treatment can lead to septic arthri-tis, subperiosteal abscess, pyomyositis, deep vein thrombosis, physeal damage with subsequent permanent impair-ment or deformity, chronic infection, septicemia, failure of multiple organ systems, and death (27). Therefore, initial evaluation of osteomyelitis should be performed as soon as possible.

Children with bone infection usually complain of pain with ambulation, fever, and focal tenderness, and sometimes redness that worsens over the course of several days. Only 36% of children have an elevated white blood cell count, but if both the erythrocyte sedimentation rate and the C reactive protein values are abnormally increased, the sensitiv-ity for infection is 98% (2).

Conventional radiographs should be the first step in the imaging evalu-ation. Although radiographs are di-agnostic in less than 20% of cases of acute staphylococcal osteomyelitis of childhood (23,28), they may be helpful

abscess is contained by the perichon-drium at the periphery of the physis, where the fibrous periosteum and the bone cortex meet in a tight junction

Figure 4

Figure 4: Metaphyseal equivalents. (a) Diagram shows that at the junction of bone and cartilage in flat bones there are areas equally predisposed to osteo-myelitis as the metaphyses of the long bones. The triradiate cartilage (arrow) is depicted in white between the two asterisks. (b) Axial fat-suppressed T2-weighted MR image of the pelvis in a 3-year-old boy with fever and right lower quadrant pain. Image shows an area of high signal intensity at the chondro-osseous junction of the right sacral wing (arrow), a metaphyseal equivalent. Additionally, there is myositis involving the right iliacus and the gluteus minimus muscles (∗).

Figure 5

Figure 5: Subperiosteal abscess. (a) Diagram demonstrates how a subperi-osteal abscess (∗) separates the periosteum (arrowhead) from the cortex. These two structures come together at the perichondrium, forming a “V” (arrow). (b) Sagittal short-tau inversion recovery (STIR) MR image in a 15-year-old boy with pain in the thigh and fever. Image of the distal femur shows a subperiosteal collection. The elevated periosteum and the cortex form a “V” with the vertex at the perichondrial junction (arrow).

to form a “V” at the vertex (Fig 5). The periosteum in childhood is critical to the blood supply of the bones, and thus stripping of the periosteum by a



on T1-weighted images (compared with the adjacent muscle) and high signal intensity on STIR or T2-weighted im-ages (Fig 6). On fat-suppressed gado-linium-enhanced T1-weighted images, bone infection usually is seen as an area of increased enhancement rela-tive to the adjacent normal marrow (Fig 6c). However, marrow enhance-ment at times can be heterogeneous or diminished compared with normal marrow. Ischemia within the areas of infected marrow, seen as areas that enhance less than normal or not at all on contrast-enhanced MR images (36), is analogous to the “cold bone scan” seen scintigraphically (34). Diminished enhancement of the marrow probably is multifactorial, related to elevated in-tramedullary pressure, vascular throm-bosis, and destruction of the periosteal blood supply. Detection of reduced marrow enhancement is important, as it indicates increased disease severity and higher risk for subsequent com-plications such as pathologic fracture

(30) and sonography to depict extraos-seous findings such as subperiosteal or soft-tissue abscess, joint effusion, and deep venous thrombosis (31,32). Sonography may show deep soft-tissue swelling as an early sign of osteomy-elitis (33). It is crucial to recognize that the current high incidence of ex-traosseous abnormalities makes scin-tigraphy alone insufficient to evaluate osteomyelitis (34). A triple-phase bone scan and magnification images when necessary, can increase sensitivity (34). At one large pediatric hospital in the United States, the cost of scintig-raphy is approximately 55% of the cost of an MR imaging examination. Scin-tigraphy usually does not require se-dation; however, its role is limited and the radiation exposure (organ-specific absorbed dose) is substantial, specifi-cally higher than 10 mGy for the bone marrow and 50 mGy for the urinary bladder (35).

An area of bone infection shows bone marrow with low signal intensity

in directing the subsequent imaging evaluation and, more importantly, show whether symptoms are the result of a different condition such as trauma or tumor. MR imaging has become the recommended modality for evaluation of a child with suspected osteomyeli-tis (29). If the child can be evaluated with MR imaging within hours of the suspected diagnosis of osteomyelitis, it is reasonable to proceed first with this modality. As more centers have MR schedules that approach 24-hour avail-ability, emergency MR imaging has be-come a reality.

The evaluation of a suspected site of infection should include a combina-tion of T1-weighted images and STIR images in the coronal or sagittal plane, axial fat-suppressed T2-weighted im-ages, and postgadolinium fat-sup-pressed T1-weighted images in axial and longitudinal planes (Fig 6). If MR imaging is unavailable, the evaluation can include a combination of scintig-raphy to detect osseous involvement

Figure 6

Figure 6: MR images in a 5-year-old girl with medial knee pain and fever. (a) Coronal T1-weighted image of the distal femur shows an ill-defined area of low signal intensity in the medial distal femoral metaphysis (arrow). (b) Sagittal STIR image shows high signal intensity in the distal femur (∗). There is also high signal intensity in the subperiosteal space (arrow) and in the adjacent soft tissues. (c) Coronal fat-suppressed gadolinium-enhanced T1-weighted image shows enhancement in the distal medial femoral metaphysis (∗) and adjacent periosteal cambium (arrow). The normal marrow of the proximal tibial metaphysis also is enhanced, although to a lesser degree.



Once the location is established or con-firmed, we perform focused high-spa-tial-resolution imaging of the affected area. In older children who are larger and longer, because of growth, imaging of the entire body becomes less prac-tical and less important. A child older than 5 years usually can describe symp-toms reliably and thus identify other sites of possible infection. Additionally, the risks of multifocality and of upper extremity involvement are less. In the group between 5 and 10 years of age, we have opted for a compromise so-lution, namely: In children with lower extremity signs and symptoms, we perform coronal STIR imaging from the pelvis to the feet, since this strat-egy is likely to demonstrate more than two-thirds of cases with unsuspected multifocal disease (Fig 10). According to Peltola et al (1), the lower extrem-ities account for 75% of the infections in children, with the femur (27%), tibia (26%), pelvis (9%) and feet being the most common locations (Fig 11). Again, this imaging approach can be accomplished in less than 10 minutes. In comparison, routine MR imaging of the entire body would take nearly twice as long and would thus be less feasible. In the group of children older than 10 years of age, it is adequate and most practical to examine only the symptom-atic area.

A triple-phase bone scan using technetium 99m (99mTc)-labeled meth-ylene diphosphonate continues to be a reasonable alternative to answer the question of multifocal disease (29). However, it does require an additional examination, it may be less readily available in an emergency situation, and it entails radiation exposure, delivering an effective dose of approximately 2.8 mSv for a 1-year-old (43). Other scin-tigraphic approaches such as imaging with the child’s white blood cells la-beled with a radiotracer, either indium 111 or 99mTc–HMPAO, are infrequently used in children (29). In the future, ra-diolabeled anti-granulocyte antibodies and antibody fragments, and radiola-beled peptides that target bacteria may provide new avenues for imaging bone infection (44).

isolated to the epiphyseal cartilage may be undetectable without the use of gadolinium enhancement (Fig 8) as even STIR and T2-weighted images have a low sensitivity for the detection of chondritis (36). Most cases of epiph-yseal osteomyelitis or chondritis occur in children younger than 4 years of age, are sometimes subacute, have few symptoms and laboratory findings, and are often caused by K kingae (Fig 9) (39). Infants infected by K kingae have milder clinical symptoms, only slightly more than one-third have an elevated white count at presentation, and 80%–90% have a modestly increased erythrocyte sedimentation rate and C reactive protein value (40). Epiphyseal osteomyelitis caused by S aureus or by Mycobacteria has more symptoms and a poorer prognosis (39).

Where Is the Infection?Establishing the location of the lesion and determining whether there is mul-tifocality is paramount for appropriate treatment (Fig 10). Blood cultures are positive in less than or equal to 40% of infected children (41), whereas bone, joint, or soft-tissue cultures have a higher yield, in the range of 70% (2). Therefore, it is important to localize the site of infection accurately to guide the diagnostic evaluation and the best site to obtain a tissue sample for cul-ture. The site of an infection usually is easy to determine in adolescents, but younger patients have fewer localizing signs and a higher risk of multifocality. A recent report questioned whether finding a second focus or any contra-lateral disease makes a difference in management (42). Although the series represents a large experience with 54 patients with proven skeletal infection, only one of these children had multifo-cal disease.

In neonates, older infants, and young children, it is reasonable to per-form whole-body MR imaging with co-ronal STIR sequences to locate the fo-cus or foci of infection. Due to the small body size in the youngest patients, this imaging approach can be accomplished in less than 10 minutes, as only one or two imaging stations are necessary.

(37); chronic osteomyelitis with subse-quent sequestra; and the need for re-peated debridement.

Infection of the Epiphyseal Cartilage and Bone in InfantsImaging of osteomyelitis in a neonate or young infant is particularly difficult, as the bone marrow is highly hemato-poietic and thus relatively rich in water and poor in fat content during the first months of life (38). As we rely on a decrease in marrow fat signal intensity on T1-weighted images to detect infec-tion, these images are ineffective for detection of infection in this young age group. STIR or T2-weighted images are also less reliable, although detection of edema signal intensity in the deep soft tissues suggests bone infection. In these children who have very little marrow fat, there is no advantage in using fat suppression, particularly for gadolini-um-enhanced images (Fig 7).

In infants, the epiphyseal cartilage can be infected with or without involve-ment of the adjacent bone. Infection

Figure 7

Figure 7: MR image in a 1-month-old boy with fever and inability to move the lower extremity. Sagittal non–fat-suppressed T1-weighted image obtained after intravenous administration of gadolinium-based contrast agent shows an area of enhancement in the proximal tibia (black arrow) that extends to the epiphysis. There is also an area of nonenhancement (white arrow) in the calf with an enhanced rim, consistent with a soft-tissue abscess.



T2-weighted images. On gadolinium-en-hanced images, the typical appearance is a nonenhanced center surrounded

intraosseous collections. An intraosse-ous abscess is seen as an area of high signal intensity in the bone on STIR or

Are There Drainable Collections?Surgical drainage is performed for mi-crobiologic diagnosis, control of the infection, and preservation of func-tion (5). MR imaging is the most re-liable modality for the evaluation of

Figure 8

Figure 8: MR images in a 4-week-old infant, born at 36 weeks’ gestation, who presented with right knee redness and swelling. (a) Axial fat-suppressed T2-weighted image of the right knee shows abundant hyperintense signal intensity within the soft tissues around the anterior portion of the knee and thickened synovium of the suprapatellar bursa (white arrow). There is discontinuity of the anterolateral epiphyseal border (black arrow) with a subtle focal area of abnormal signal intensity within the epiphyseal cartilage (∗). (b) Axial fat-suppressed T1-weighted image obtained after intravenous contrast agent administration shows an avascular area within the anterolateral epiphyseal cartilage (arrow) that is contiguous with the joint effusion. There is diffuse enhancement of the surrounding soft tissues. (c) Sagittal fat-suppressed T1-weighted image obtained after intravenous contrast agent administration shows the focal area of epiphyseal cartilage infection (arrow) and associ-ated septic arthritis. Citrobacter braakii was eventually isolated from a cartilage biopsy.

Figure 9

Figure 9: Coronal fat-suppressed gadolinium-enhanced T1-weighted MR image in a 10-month-old girl with distal humeral osteomyelitis due to K kingae. There is abnormal enhancement in the cartilage of the capitellar epiphysis (arrow) and in the articular and periarticular soft tissues. (Image courtesy of Jie Nguyen, MD.)

Figure 10

Figure 10: MR images in a 7-year-old boy with fever, limping, and right leg pain. (a) Coronal T1-weighted image shows marked irregularity of the signal intensity in the marrow of the distal tibial metaphysis, consistent with osteomyelitis. (b) Coronal STIR image of the pelvis in the same patient shows increased signal intensity (arrow) in the right ischiopublic region consistent with a second focus of infection. There is an abscess within the obturator externus muscle lateral to the focus of infection.



periosteum and the bone and is of low or mixed echogenicity (Fig 12) and of high signal intensity on T2-weighted or STIR images. The identification of the “V” configuration, where the elevated periosteum and underlying bony cor-tex meet at the perichondrium (Fig 5), defines the location of an abscess as being in the subperiosteal space rather than in the adjacent soft tissues. On T1-weighted images of subperiosteal collections, high-signal-intensity globu-lar structures within the abscess cor-respond to fat globules (Fig 13) (47). These are mainly seen in older children and are formed by the lytic effect of the bacterial enzymes or ischemic insult on the bone marrow fat, with subsequent adipocyte lysis and release of intracellu-lar fat. Detection of fatty globules, or in some cases a fat-pus layer, is important

by a rim of enhanced tissue (45). Since enhancement is a reflection of vascular supply, it is likely that antibiotics will not penetrate sites where the intrave-nous contrast material does not. Al-though abscesses can be seen consis-tently on STIR or T2-weighted images, the confidence for detection of purulent collections increases with the use of in-travenous contrast material (46).

Subperiosteal collections are de-picted well with sonography and MR imaging (22). The key structures to identify are an elevated fibrous layer of the periosteum, which is separated from the underlying bone cortex by pus. The fibrous layer of the perios-teum appears as an echogenic line at sonography and as a hypointense linear structure at MR imaging. The subperiosteal fluid lies between the

Figure 11

Figure 11: Relative frequency of osteomyelitis in the different bones including all pediatric age groups. Osteomyelitis affects more commonly the fast growing areas and involves the lower extremities more than the upper ones. (Modified from references 1,2.)

Figure 12

Figure 12: Subperiosteal collection in an 8-year-old boy with proximal fibular osteomyelitis. Sonogram demonstrates the elevated echogenic periosteum (black arrow) and the sonolucent sub-periosteal collection between the periosteum and the cortex (white arrow).

Figure 13

Figure 13: Subperiosteal abscess with fat globules in a 7-year-old boy with a left distal fibular osteomyelitis. Coronal T1-weighted MR image shows the low signal intensity periosteum (black arrow) converging with the bone at the perichon-drium. More cephalad, a subperiosteal collection is seen to contain high signal intensity (fat) globules (white arrows).



with osteomyelitis (51), epidural ab-scess may be the only abnormality. Paraspinal abscess formation may also occur, with or without threat to the central nervous system. Infections can be low grade and produce only chronic back pain and disk destruction. These infections typically are caused by S au-reus and are unlikely to result in epi-dural involvement (52). There is in-creasing evidence that K kingae may be responsible for spondylodiscitis in infants (53).

Radiographs, obtained in part to exclude other pathologic conditions, may show disk space narrowing, ef-facing or sclerosis of the endplates, and alignment abnormalities. Multiple levels are involved in 6% of the cases, and skip lesions are seen in 3% (50). Contrast-enhanced MR imaging should be obtained in all patients suspected of having a spinal infection. In osteomye-litis there is abnormality in the signal intensity of the disk and the adjacent endplates, with paraspinal edema signal intensity or frank abscess. If there are neurologic findings, it is paramount to search for evidence of a spinal epidural abscess (54). An epidural abscess oc-curs in slightly more than one-third of cases of spondylodiscitis and is seen as a ring-enhancing lesion within the epi-dural space, with or without cord com-pression (50). Because of the frequency of noncontiguous skip lesions, it is ad-visable to image the entire spine. Sur-gery is indicated if there are neurologic deficits, spinal instability, or inadequate response to antibiotics (51).

Pelvic OsteomyelitisPelvic osteomyelitis occurs more fre-quently in older children (mean age, 10 years) (55), but the clinical evalua-tion is difficult because the presenting symptoms can mimic other pathologic conditions. The clinical presentations vary: Infection near the sacral roots can produce nerve irritation and therefore present with a lumbar disk syndrome. Infection in the gluteal region can man-ifest as a subgluteal abscess, and infec-tion in the ilium that extends into the iliac fossa can present with abdominal pain. In our experience some patients

This study suggests that whether or not an abscess requires drainage can be decided based on the clinical scenario, particularly the response to antibiotics (33). A more recent study suggested that soft-tissue collections larger than 2 cm in diameter usually do not resolve with antibiotics alone and require per-cutaneous drainage or surgery (49).

Specific Locations

Spinal OsteomyelitisVertebral osteomyelitis has a bimodal incidence: There is one peak in early childhood and another one in the 6th decade (50). The incidence appears to be increasing, and this is believed to be related to the increased utilization of intravascular devices and intravenous drug abuse (51). The disease begins in the vicinity of the vertebral body end-plate, where there is a metaphyseal equivalent. Bacterial infections involv-ing the spine almost always affect the disk space. The most severe cases can extend into the epidural space and re-sult in rapid neurologic deterioration and permanent sequela if not treated immediately. Although most (86%) epi-dural abscesses occur in association

because it defines the subperiosteal ab-normality as an abscess and can help differentiate it from other subperiosteal process such as tumor.

In bones with subperiosteal collec-tions, T1-weighted images often show diffuse heterogeneity of the bone mar-row signal intensity, with relatively di-minished enhancement following intra-venous contrast agent administration compared with unaffected bone (Fig 14). This same phenomenon has been de-scribed on bone scans, in which a sub-periosteal abscess is suspected when there is decreased tracer uptake in bone. Both modalities presumably re-flect ischemia of bone, which has re-sulted from the stripping of periosteal blood vessels by the purulent collection (48). Sonography allows serial mea-surements of the subperiosteal abscess, which may guide management, partic-ularly in children who fail to respond adequately to therapy.

How large must an abscess be be-fore it needs drainage? The literature regarding guidelines for drainage of ab-scesses is both limited and conflicted. In one study that utilized sonography in 38 subjects with osteomyelitis, subperios-teal abscesses up to 3 mm in diameter resolved successfully without surgery.

Figure 14

Figure 14: Osteomyelitis of the distal tibial metaphysis in 7-year-old boy. (a) Coronal T1-weighted MR image shows diffuse irregularity of the bone marrow in the distal metaphysis and a low signal intensity subperiosteal collection with high signal intensity fat globules within the collection (arrows). (b) Sagittal gadolinium-enhanced fat-suppressed T1-weighted image shows areas of decrease enhancement in the bone marrow (arrows) related to the infectious process.



to recognize that septic arthritis of the hip, regardless of the presence of coex-isting osteomyelitis, is associated with decreased epiphyseal perfusion in more than 80% of cases (61).

It is imperative to identify deep ve-nous thrombosis, as pulmonary emboli occur in almost half of children who have osteomyelitis and deep venous thrombosis (62,63) (Fig 16). Deep venous thrombosis occurs almost ex-clusively in the vicinity of the infected bone or in association with central ve-nous catheters. Thus, when evaluating cross-sectional images of the bone infec-tion, it is imperative to look for thrombi in the adjacent veins. In children with osteomyelitis who (a) are critically ill at presentation, (b) have important pul-monary findings, or (c) are persistently bacteremic with MRSA, sonographic evaluation for deep venous thrombosis should be performed of and adjacent to the site or sites of infection.

Delayed complications from acute osteomyelitis include growth arrest, fracture, and chronic osteomyelitis. In slightly more than one-fourth of cases of osteomyelitis, there is focal destruc-tion of the physis, which allows for-mation of a bridge of bone. This bony bridge tethers the epiphysis to the me-taphysis and disrupts normal growth. MR imaging can depict the bony bridge as early as 6 months after the infec-tion. Fortunately, many children with physeal involvement show resolution of the physeal insult with adequate antibiotic therapy (64,65). A recently observed phenomenon is the develop-ment of pathologic fractures. In a series composed primarily of children with MRSA infections, patients with initial MR images showing a sharp zone of de-creased bone marrow enhancement, or subperiosteal abscess more than half of the bone circumference, had increased incidence of fracture 2 months later (10,37).

If on unenhanced T1-weighted im-ages an abscess reveals a discrete pe-ripheral zone of relatively higher signal intensity compared with the central cavity or the surrounding reactive mar-row, subacute osteomyelitis should be suspected. This halo of relatively higher

discrete fashion across the physis, or it can course parallel to the physis in a much broader zone. In both instances, once physeal involvement is detected it is important to reimage 3–6 months later to detect early transphyseal bony bridge formation that ultimately can lead to limb deformity (Fig 15).

Additional Imaging Findings

It is important to identify complications of osteomyelitis that occur during the acute infection and those that develop later in the course of the disease. The initial focus of osteomyelitis can extend into the adjacent medullary cavity, in-vade the subperiosteal space and sur-rounding soft tissues, as well as cross the adjacent physis into the epiphysis and possibly the joint (Fig 1). Exten-sion of the infection into the soft tissues can result in cellulitis or myositis, both of which may develop into an abscess of the soft tissues or muscles (Figs 7, 10b), particularly in the pelvis. In re-cent years there has been an important increase in the incidence of thrombo-phlebitis, which now occurs in 10%–30% of cases, typically in association with MRSA infection (56,57). At times the infection can result in septic emboli to the lungs and the brain (Fig 16).

Infections of the intracapsular por-tion of the proximal femoral metaphysis or of the periarticular pelvis can extend into the hip joint. Recent studies have shown that up to 60% of patients with a clinical picture suggestive of septic ar-thritis of the hip have pelvic osteomye-litis (58,59). In patients with suspected septic arthritis and more than three predictive factors of bone infection (age . 3.6 years, symptoms such as fever, or non–weight-bearing for more than 3 days, high C-reactive protein level, low platelet count, and elevated absolute neutrophil count) (39,58–60), it is justified to obtain MR images of the pelvis to exclude osteomyelitis. It is not possible by using imaging to re-liably differentiate a reactive effusion from septic arthritis, and when there is a sizable effusion in the vicinity of a focus of bone infection, the joint fluid should be aspirated. It also is essential

have undergone sonography or com-puted tomography (CT) first for eval-uation of suspected right lower quad-rant disease. Radiographs are almost always unrevealing. Pelvic osteomyelitis is associated with substantial soft-tissue inflammation in 85% of cases and ab-scesses in 55% of cases (49) (Fig 10b). For this reason, it is important to im-age the soft tissues adequately. Since the bone abnormality often is rela-tively small compared with the extent of soft-tissue involvement, the focus of osteomyelitis can remain undetected, which results in a misleading diagnosis of myositis or a soft-tissue abscess. It is important to search for small areas of abnormal marrow signal intensity in metaphyseal equivalent locations (Fig 4b). Another clue to the existence of pelvic osteomyelitis is the presence of subperiosteal collections that are rela-tively small and subtle in this region.

Periphyseal OsteomyelitisA metaphyseal focus of infection can extend to involve the physis. Transphy-seal extension can occur in as many as 80% of cases (55). The infection can extend from the metaphysis in a small,

Figure 15

Figure 15: Sagittal fat-suppressed gadolinium-enhanced T1-weighted MR image in a 4-year-old with knee pain, limping, and fever for 4 days. Image shows a focus of infection extending from the me-taphysis, across the physis, and into the epiphyseal cartilage. There is also extension of the process into the subperiosteal space and enhancement of the synovium indicative of septic arthritis.



no fluorodeoxyglucose uptake despite showing persistent changes on MR im-ages (69). Since fluorodeoxyglucose up-take becomes normal 3–4 months after surgery or trauma, it also helps to dif-ferentiate residual postsurgical changes from persistent infection (69,70). It is likely that PET/MR imaging will have an important role in the imaging of complex cases of osteomyelitis, but its role is not yet established (71).

Is It Something Different than Osteomyelitis?

Several conditions that can present with fever, extremity pain, and radiographs showing aggressive bone destruction can mimic acute osteomyelitis. Tumors include metastatic neuroblastoma and Langerhans cell histiocytosis (LCH) in children less than 5 years of age, and leukemia, Ewing sarcoma, and osteosarcoma in older children. Most of these lesions present with bone destruction, often accompanied by a

development of a cloaca, from the Latin word sewer, which is a linear defect in the bone that penetrates the cortex and allows for spontaneous drainage of pu-rulent material. A sinus tract is a chan-nel lined with granulation tissue that allows pus to drain from the infected bone to the skin surface (29).

If symptoms persist after therapy, it becomes difficult to determine whether an infection is active or not. Increased signal intensity on STIR or T2-weight-ed images, increased enhancement following intravenous contrast agent administration, and increased scinti-graphic uptake can persist for months following the resolution of the infec-tion. Positron emission tomography (PET) imaging seems to be the most reliable technique for evaluation of chronic bone infection. In a recent series, PET imaging was shown to be superior to MR imaging for distinguish-ing between active infection and healing in these children, as successfully treat-ed osteomyelitis had only minimal or

signal intensity has been termed “the penumbra sign” (Fig 17) (66,67).

A Brodie abscess is a limited area of subacute osteomyelitis. It is charac-terized by a central area of necrosis, surrounded by a well-defined, sclerotic inner rim that in turn is surrounded by a halo of reactive tissue. A Brodie abscess should be differentiated from the nidus of an osteoid osteoma. A nidus may contain sclerotic material and is highly vascularized. In contra-distinction, a Brodie abscess generally lacks sclerotic material and is avascu-lar. An elongated lesion is more likely to be an abscess than a tumor.

Chronic osteomyelitis, character-ized by symptoms of infection that last more than 6 months, occurs more fre-quently in developing countries (68). Chronic infection results in necrotic bone, termed a sequestrum, surround-ed by pus and a reactive bone sclerosis, called the involucrum. On MR images, the cortex shows high signal inten-sity and thickening. At times, there is

Figure 16

Figure 16: MR images in a 9-year-old girl with pain in the leg and abdomen. (a) Coronal fat-suppressed gadolinium-enhanced T1-weighted image shows decreased enhancement in the right tibial metaphysis compared with the left, consistent with osteomyelitis. There is an adjacent abscess (arrow) in the soft tissues. (b) Sagittal fat-suppressed gadolinium-enhanced T1-weighted image of the thigh shows a nonenhanced clot (arrow) occupying the majority of the right deep femoral vein. (c) Coronal fat-suppressed gadolinium-enhanced T1-weighted image of the abdomen shows an area of consolidation abutting the periphery of the right hemi-diaphragm. A CT angiogram (not shown) demonstrated that the child had multiple pulmonary emboli and peripheral infarcts.



In sickle cell disease, it is very dif-ficult to differentiate between infection and infarction (vaso-occlusive crisis). Children with osteomyelitis present with a longer duration of pain, fever, and swelling than patients with sickle cell disease and vaso-occlusive crises. If more than one site is affected, vaso-occlusive crisis is more likely (80). The major problem from the standpoint of imaging is that infarction and infection can coexist and their imaging findings overlap. A recent study (81) attempted to differentiate infection from infarc-tion by using MR imaging with fat-sup-pressed T1-weighted images. With this sequence, stagnant blood in an infarc-tion has high signal intensity, whereas infected, edematous marrow has low signal intensity. Differentiation was not possible, because in the few cases in which infection was demonstrated, in-fection developed in areas of infarction. On the other hand, it is well known that infection can produce bone ischemia even in individuals without sickle cell disease (14). Another major challenge is that infarction is nearly 50 times more common than infection in patients with sickle cell disease (80). Evaluation of the performance of any modality is hindered by the fact that the pretest probability is much greater for infarction than with infection. Scintigraphic evaluation is based on a combination of bone marrow imaging using 99mTc sulfur colloid and bone scanning using 99mTc methylene diphosphonate (82). In the series by Skagg et al, infarcts showed no uptake on the marrow scans whereas infections showed increased uptake on bone scans but normal activity on marrow scans. Although the authors were successful in diagnosing four cases of osteomyelitis, the technique assumes that infarction and infection do not coexist (which they can), and the combination of both bone and marrow studies delivers a consid-erable amount of radiation (83). Simi-lar to infection, infarction can produce edema of the bone and adjacent soft tissues, subperiosteal fluid collection, and bone destruction (84). Therefore, differentiation between infection and in-farction on the basis of detecting fluid in osteomyelitis at either MR imaging or

malignancies such as osteosarcoma usually have a sharper margin between the affected and the unaffected mar-row on T1-weighted images (73).

Any disease that causes marrow in-filtration, inflammation, or edema can be confused with osteomyelitis. The most difficult differentiation is between infectious osteomyelitis and chronic nonbacterial osteomyelitis (CNO), par-ticularly its most severe form, termed chronic recurrent multifocal osteo-myelitis (CRMO). The differentiation between an infectious process and CRMO is particularly difficult in the extremities (74). Both of these condi-tions produce bone destruction, pri-marily affect the metaphyses and me-taphyseal equivalents, and can extend into the physis. With CNO/CRMO, symptoms typically are less acute and involvement is frequently multi-focal (more than 80% of cases) (75) and often symmetric (76). The most common sites of involvement in CNO/CRMO are the pelvis, lower extrem-ities, shoulders, and spine (77). In the tubular bones, nearly 90% affect the physis (77). Unlike hematogenous os-teomyelitis, CNO/CRMO often involves the clavicle. Lesions of CNO/CRMO in the axial skeleton usually show only mild marrow edema without soft-tissue edema, which is unlike bacterial oste-omyelitis. Inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate are only mildly el-evated in CNO/CRMO (78). In recent years there has been great interest in using a clinical score that can help dif-ferentiate between osteomyelitis and CNO/CRMO, thus avoiding biopsies (79). The parameters that predict CNO/CRMO are as follows: normal blood cell count (odds ratio [OR], 81.5); symmetric bone lesions (OR, 30.0); lesions with marginal sclerosis (OR, 26.8); normal body temperature (OR, 20.3); lesions in the vertebra, clavicle, or sternum (OR, 13.9); more than one radiologically proven lesion (OR, 10.9); and C-reactive protein level greater than 1 mg/dL (OR, 6.9). This score has shown to have a positive predictive value of 97% and a sensitiv-ity of 68% (79).

soft-tissue mass. The clinical presen-tation can overlap, as children with infections and tumors can have fever and localized bone findings. However, a tumor often is associated with longer symptom duration. Although the plain radiographic findings can sometimes overlap, it is important to underscore that radiographically detectable bone destruction is a late finding in osteomy-elitis and that patients typically have experienced symptoms for more than a week before findings become appar-ent. On MR images, osteomyelitis is not associated with a discrete mass. In younger children, LCH can result in dramatic bone destruction and perile-sional edema. However, unlike osteo-myelitis, LCH is primarily diaphyseal (72). On MR images of osteomyelitis, there is abundant perilesional edema that extends along the marrow and into the soft tissues. This extension re-sults in an ill-defined margin between normal and abnormal marrow, which fades away from the center of the infection. Ewing sarcoma and other

Figure 17

Figure 17: Sagittal T1-weighted MR image in a 17-year-old patient with bone lesion in the right proximal humerus and concern for malignancy. Image shows a penumbra sign, which consists of a relatively high-signal-intensity halo (white arrow) between the low-signal-intensity abscess (∗) and the low-to-intermediate signal intensity sclerotic edematous bone (black arrow).



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one or more areas of infection, the loca-tion of the infection, and, in some cases, whether there are collections of pus large enough to require drainage (87).

Conclusion

The imaging approach to acute hema-togenous osteomyelitis in children has to be directed not just to the detection of the primary focus of infection but also to the evaluation for collections of pus in the subperiosteal space, soft tissues, and joints. Bone infection, par-ticularly by S aureus, is associated with disease in those areas and with adja-cent thrombophlebitis. It also is impor-tant to detect concomitant foci that also may require drainage. Infection caused by K kingae is recognized more often and typically involves the epiphyses of infants and young children (88).

Disclosures of Conflicts of Interest: D.J. dis-closed no relevant relationships. J.P.D. disclosed no relevant relationships. J.D. disclosed no rel-evant relationships. T.L. disclosed no relevant relationships. J.W.S.G. disclosed no relevant relationships.

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Figure 18

Figure 18: MR image in an 11-year-old girl with sickle cell disease who presented with acute right lower extremity pain and fever. (a) Coronal STIR and (b) axial fat-suppressed T2-weighted images show a subperi-osteal fluid collection (white arrow) and diffuse myositis (black arrows). Following negative blood cultures and more than a year of follow-up, the clinical diagnosis was consistent with bone infarct.



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Hematogenous osteomyelitis in infants and Children: Imaging of a … · 2017-05-31 · ical manifestations and management, we must adjust the imaging approach to the disease. In this