Review article

Chronic recurrent multifocal osteomyelitis: typical patterns of bone involvement in whole-body bone scintigraphy Gunsel Acikgoz and Lauren W. Averill Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of unknown etiology. It affects children and adolescents predominantly and occurs mostly in the female population. It is characterized by the insidious onset of pain and swelling, with a fluctuating clinical course of relapses and remissions. Typically, several bones are affected, either synchronously or metachronously, and bilateral involvement is common. CRMO most commonly affects the metaphysis of long bones, especially the tibia, femur, and clavicle. The spine, pelvis, ribs, sternum, and mandible may also be affected. Although lesions are mostly multiple, patients may present with a single symptomatic focus. Radiographic findings may be negative early in the course of the disease. Bone scintigraphy is useful in determining the presence of abnormality and the extent of disease. The imaging and clinical features of CRMO overlap with those of infectious osteomyelitis, bone malignancy, and inflammatory arthritis.

Introduction Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disease characterized by sterile osteomyelitis. Most patients present with multiple and recurrent lesions; however, unifocal or nonrecurrent patterns have also been described. This entity was first described by Giedion and colleagues in 1972. They presented a report on four children who had clinical, radiologic, and histologic evidence of osteomyelitis without bacterial growth from tissue and blood cultures. They drew attention to multiple, symmetrical lesions, mainly around the growth plates of the long bones, and named the condition ‘subacute and chronic symmetrical osteomyelitis’ [1]. Probst and colleagues [2,3] reported on other children with similar clinical and imaging features and first used the term CRMO in 1978. Since then, several other names have been used to describe this disorder, including chronic nonbacterial osteomyelitis; nonbacterial osteitis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. The terms CRMO and chronic nonbacterial osteomyelitis are often used interchangeably. The acronym SAPHO is more frequently used in adult patients with sterile osteomyelitis and joint and skin inflammation, but this constellation is uncommon in children. It is not yet clear whether CRMO and SAPHO are different ends of a disease spectrum or separate entities [4–7]. There are no pathognomonic signs or specific diagnostic tests for CRMO. The diagnosis is established by 0143-3636 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

Nonetheless, CRMO can be confidently diagnosed with the recognition of typical imaging patterns in the appropriate clinical setting. This article reviews imaging findings with special emphasis on bone scintigraphy and specific disease sites. Nucl Med Commun 35:797–807 © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Nuclear Medicine Communications 2014, 35:797–807 Keywords: bone scintigraphy, chronic osteomyelitis, chronic recurrent multifocal osteomyelitis, nonbacterial osteomyelitis Department of Medical Imaging, Nemours/Alfred I. duPont Hospital for Children, Wilmington, Delaware, USA Correspondence to Gunsel Acikgoz, MD, Department of Medical Imaging, Nemours/Alfred I. duPont Hospital for Children, P.O. Box 269, Wilmington, DE 19899, USA Tel: + 1 302 651 4641; fax: + 1 302 651 4476; e-mail: [email protected] Received 24 February 2014 Accepted 9 March 2014

exclusion of infectious osteomyelitis, malignancy, and other diseases on the basis of clinical, imaging, microbiologic, and often histological findings. The role of imaging is pivotal in the evaluation of CRMO; therefore, awareness of the imaging specialist on the various presentations of CRMO may facilitate early diagnosis and appropriate treatment of the disease. There are multiple reports focusing on the patterns of CRMO on radiographs and MRI images. There is, however, a paucity of literature reviewing the spectrum of bone involvement using bone scintigraphy. In this article, we present a brief review of the epidemiology, etiology, histopathology, and clinical features of CRMO. We describe the imaging appearance of CRMO with special emphasis on bone scintigraphy and specific disease sites. Common epidemiologic and clinical features

CRMO mostly affects children between the ages of 2 and 17 years, with a mean age of 10 years. However, infant and adult forms also have been described. Most cohorts or case series report an approximately 2 : 1 female-tomale ratio. The presentation is heterogeneous, and the course is unpredictable. Patients generally complain of bone pain, which may be worse at night. Swelling of the affected area is inconsistently seen. Systemic symptoms, such as fever, malaise, and weight loss, may or may not be present. Laboratory investigations often show a mildly elevated erythrocyte sedimentation rate, although the DOI: 10.1097/MNM.0000000000000126

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erythrocyte sedimentation rate may be higher if there are comorbid autoimmune diseases. Tumor necrosis factor-α and C-reactive protein levels may also be elevated. The white blood cell count, though, is usually within normal range. The disease is marked by exacerbations and remissions over years [5,7–9]. The outcome is good for most children, with resolution of CRMO without permanent sequelae. However, permanent bone deformity can occur, especially due to pathologic fractures such as vertebral compression deformities with consequent scoliosis and leg length discrepancy. Functional or cosmetic sequelae may develop because of hyperostosis [10,11]. Anywhere between one and more than 20 sites, with a mean of three to four sites, can be involved at one time during the disease course [7,8,12]. Bone lesions can be distributed throughout the axial and appendicular skeleton, but most lesions are located in the metaphyses of long bones and metaphyseal equivalents. Among long bones, there is a predilection for the lower extremities, with the distal femur and proximal or distal tibia being most commonly affected. Other common areas of involvement include the vertebrae, pelvis, and clavicle. Less frequently, the mandible, ribs, small bones of the hands and feet, scapula, and sternum can also be involved [8,13,14]. In one series, mandible involvement was most common among patients with unifocal disease [7]. Although lesions are multifocal in ∼ 80% of cases, the initial symptoms may manifest only in one location [5,7,8,13]. Most patients respond to NSAIDs. Corticosteroids may be indicated in some patients. Successful treatment with bisphosphonates, methotrexate, sulfasalazine, azithromycin, colchicines, interferon, anakinra, and antitumor necrosis factor agents has been reported in a small series. Several other pharmaceutical agents have been described in case reports [6,7]. Etiologic factors and histology

The etiology and pathophysiology of CRMO are poorly understood. Initial reports described isolation of organisms such as Staphylococcus epidermidis and Propionibacterium spp. from biopsied lesions. However, these are now thought to represent contaminants rather than causative bacteria. The more recent, larger cohorts have not identified evidence of a microbial etiology by culture or PCR amplification [4,9]. In addition, antibiotic therapy does not alter disease course. Currently, CRMO is thought to be in the spectrum of autoimmune and autoinflammatory disorders. This assertion is supported by the association of CRMO with multiple autoimmune diseases, particularly palmoplantar pustulosis, psoriasis, and inflammatory bowel disease, in patients and family members, as well as by its response to corticosteroids [6,15]. There is also evidence implicating a genetic predisposition. Two rare monogenic syndromic forms of CRMO have been identified. An autosomal-recessive syndrome,

called Majeed syndrome, is characterized by early-onset CRMO and dyserythropoietic anemia, with or without neutrophilic dermatosis (Sweet syndrome). Mutations in the LPIN2 gene have been identified as the cause of Majeed syndrome. Another monogenetic form of CRMO, termed deficiency of the interleukin-1 receptor antagonist, has been recognized more recently. Caused by mutations in the IL1RN gene, deficiency of the interleukin-1 receptor antagonist is an autosomalrecessive, potentially life-threatening, autoinflammatory disorder that presents during the neonatal period with generalized pustulosis, osteitis, periostitis, and systemic inflammation [6,16]. Histological examination of CRMO lesions shows nonspecific acute, subacute, or chronic osteomyelitis. Early lesions show an acute inflammatory process with a predominance of polymorphonuclear leukocytes and osteoclastic bone resorption. Later, chronic inflammation with lymphocytic infiltrates and new bone formation dominates the lesion. Marrow fibrosis, osteonecrosis, granulomas, and hyperostosis may occur [4,17–19]. Some case reviews reported poor correlation between the histologic findings and the clinical duration of the disease; however, this is likely related to exacerbations and remissions during the disease course, as well as sampling limitations inherent to needle biopsy [14,20]. Imaging findings

Most patients are initially evaluated by plain radiography. Although the radiographic appearance of lesions can be purely osteolytic, purely sclerotic, or mixed, the classic radiographic description is a juxtaphyseal, mixed osteolytic and sclerotic lesion. In early stages, there is typically an osteolytic lesion within the metaphysis adjacent to the growth plate. Surrounding sclerosis usually develops over time. Localized or diffuse hyperostosis or periosteal reaction may also be seen; however, there is no periosteal elevation or sequestrum formation that is often seen with pyogenic osteomyelitis [7,8,13,14,18,21–23]. Lesions of CRMO may be occult on radiographs. In addition, plain radiography is nonspecific and not sensitive for detecting active inflammation or asymptomatic sites. Because the disease is multifocal in most cases, detection of clinically silent lesions is very helpful in making the correct diagnosis. Evaluation of the whole body by bone scintigraphy or MRI is recommended when CRMO is suspected [13,14,22]. The role of computed tomography is limited in the diagnosis of CRMO. It can be used to detect subtle bone destruction and to follow up lesions, particularly in anatomically difficult sites, such as the mandible, sternum, spine, and pelvis [14]. Bone scintigraphy using methylene diphosphonate or hydroxymethylene diphosphonate labeled with technetium-99m is extremely useful in identifying symptomatic lesions and in documenting the multiple asymptomatic

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lesions of CRMO [13,24,25]. Bone scintigraphy is especially useful in areas that are difficult to evaluate with plain radiography, such as the pelvis and vertebrae [5]. The lesions of CRMO show hyperemia on the early softtissue-phase images and focal increased uptake on delayed images. The growth plate involved may appear widened or blurred in the early or delayed phases of bone scintigraphy. The soft-tissue-phase images have an added value in localization of small juxtaphyseal lesions and subtle bilateral metaphyseal involvement. Singlephoton emission computed tomography (SPECT) and pinhole imaging also aid in the detection of abnormal sites [13]. Bone scintigraphy can help target biopsy to the most active lesion and may also identify a more easily accessible lesion than the presenting site, which is clinically important as most patients undergo confirmatory biopsy. During treatment and follow-up, bone scintigraphy is useful for monitoring disease activity, with a reduction or resolution of the increased uptake seen in quiescent lesions [25]. Bone scintigraphy has been shown to be very sensitive for the detection of lesions of CRMO. An early report by Mortensson et al. [24] asserted that bone scintigraphy can identify all symptomatic sites. In a report by Demharter et al. [25], bone scintigraphy was seen to be positive in 23 of 24 lesions observed radiographically. Mandell et al. [13] reported excellent sensitivity of whole-body bone scintigraphy in a series of 14 children with CRMO, in which they detected at least one lesion in each child (1–18 lesions). Most children in this study presented with a single site of pain, but bone scintigraphy demonstrated multifocal disease in most. In a fourth study, published in 2012, involving a large cohort of 70 patients diagnosed with CRMO, 57 patients underwent bone scintigraphy. Among them, 96% had a positive bone scintigraphy finding corresponding with the clinically suspected site of involvement [7]. Bone scintigraphy can also reveal clinically or radiologically silent lesions. Demharter et al. [25] performed bone scintigraphy in five patients during the time of initial diagnosis of CRMO or during follow-up. Bone scintigraphy revealed 14 clinically silent foci and eight foci that were occult on plain radiographs. Although bone scintigraphy is an excellent tool for identifying symptomatic sites as well as clinically silent lesions, a few authors have reported slightly reduced sensitivity of the technique compared with MRI in the evaluation of spinal, pelvic, and femoral lesions [8,26,27]. Morbach et al. [27] compared whole-body bone scintigraphy with MRI in 32 patients by performing wholebody MRI in 14 patients and localized MRI in the other 18 patients. One or more lesions were documented in all 32 patients (100%) with MRI compared with visualization in 30 of 32 patients (94%) with bone scintigraphy. However, when only symptomatic sites were evaluated, MRI detected inflammation in 53 of 54 regions (94%), whereas bone scintigraphy detected disease in 40 regions

(74%). Morbach et al. [27] attributed the lower sensitivity of bone scintigraphy to the inferior spatial resolution of planar scintigraphy in detecting metaphyseal lesions with physiological radiotracer uptake in the adjacent growth plate, in particular symmetric lesions. In this study, though, the technical details of bone scintigraphy have not been described in detail. It is unclear whether they performed whole-body blood pool imaging, previously shown by Mandell et al. [13] to increase the sensitivity of bone scintigraphy in detecting silent lesions and metaphyseal lesions. Targeted MRI of a specific area has been shown to have excellent sensitivity in detecting early medullary bone involvement and the extent of the lesion of CRMO. During the active phase, MRI findings are characterized by edema-like lesions, which appear hypointense on T1-weighted images and hyperintense on T2-weighted and short tau inversion recovery (STIR) images, and show enhancement after contrast administration. Because of the development of sclerosis, signal intensity diminishes on both T1-weighted and T2-weighted sequences during the quiescent phase of the disease. MRI can show associated soft-tissue involvement, such as periostitis, synovitis, and myositis. However, there is no abscess, sequestrum, or sinus tract formation, which are features of bacterial osteomyelitis [8,14,22,23,28–30]. In a retrospective study by Falip et al. [8], 42 long bone sites were investigated with localized MRI, and bone marrow edema was found in all cases. Progress in MRI technology and increasing emphasis on radiation dose reduction have made whole-body MRI the modality of choice for imaging in pediatric patients with known or suspected systemic musculoskeletal disorders, including CRMO. Fritz et al. [23] reported abnormal hyperintensity on STIR images and contrast enhancement on T1-weighted images in all CRMO lesions of 13 children who underwent whole-body MRI. They found conspicuity of osseous lesions to be similar on the STIR images and the contrast-enhanced, fat-suppressed, T1-weighted fast spin echo images. Therefore, they suggested the use of contrast agents only in the initial assessment of patients to increase the conspicuity of inflammatory arthropathy or abnormalities of nonmusculoskeletal organ systems [23]. More recently, Falip et al. [8] reported contrast administration to be unnecessary during whole-body MRI for evaluation of CRMO but helpful during standard localized MRI for ambiguous lesions, such as those with a pseudoabscess pattern. They suggested an MRI protocol including whole-body T1-weighted (either a gradientecho or a turbo spin echo technique) and STIR imaging in the coronal planes to detect most lesions [8]. Wholebody diffusion-weighted MRI is a promising MRI application that allows contrast-free, rapid, and reliable assessment of osseous and soft-tissue lesions and may also have the potential to differentiate neoplasms from inflammatory musculoskeletal lesions and abscesses

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in situations such as vertebral body fractures [31]. However, the role of diffusion-weighted MRI in CRMO detection is yet to be investigated. Although whole-body MRI is gaining importance as a radiation-free technique and appears to be more sensitive than bone scintigraphy in the detection of CRMO lesions, specificity and clinical importance of the MRI-positive but bone scintigraphy-negative lesions are still contentious issues [27]. An MRI performed only in the coronal plane may miss bone lesions located extremely anteriorly or posteriorly, such as those of sternoclavicular and costovertebral joints [32]. MRI is more susceptible to motion artifacts compared with bone scintigraphy; therefore, sedation is more frequently utilized. The age-related conversion of hematopoietic marrow to fatty marrow in children may create a confusing appearance on MRI and may be misleading. Further, whole-body MRI is not as widely available and is considerably more expensive than bone scintigraphy. It is important to recognize the pitfalls of bone scintigraphy to help the rapid and accurate diagnosis of CRMO. On bone scintigraphy, symmetric juxtaphyseal or metaphyseal lesions may be less evident on the delayed planar images, but the soft-tissue-phase images help to localize these lesions. Thus, blood pool imaging should be performed as part of the standard bone scintigraphy workup. Because multifocal involvement is seen in more than 80% of cases, it is important to perform whole-body blood pool and delayed imaging, even though most patients present with a single symptomatic site. Sensitivity of bone scintigraphy may also be increased with the use of pinhole, SPECT, or SPECT/computed tomography techniques. Imaging appearance Long bones

The long bones of extremities are the most common site of involvement, either during initial presentation or during relapses. In a review of 31 children with CRMO, 77% of patients had at least one long bone lesion, which was either in the tibia or in the femur in 83% of those patients [8]. In a large cohort of 70 pediatric CRMO patients, there was tibial involvement in 41%, femoral involvement in 29%, and fibular involvement in 21% of patients. Upper-extremity involvement was less common: humerus in 14%, radius in 4%, and ulna in 1% [7]. Although up to 90% of lesions are centered in the metaphysis, epiphyseal and diaphyseal extension may be seen (Figs 1 and 2). Exclusively epiphyseal or diaphyseal involvement is rare. Bilateral involvement is common, although imaging findings and clinical stages of bilateral lesions may vary [8]. Pelvis

CRMO of pelvic bones is common and reported in ∼ 30% of pediatric case series [7,8]. Recently, however, Von

Kalle et al. [12] reported pelvic bone involvement in 41 of 53 (77%) pediatric cases evaluated using whole-body MRI. Similar to bacterial osteomyelitis, there is predilection for metaphyseal-equivalent sites, such as synchondroses and sacroiliac joints (Fig. 3). Because activity of synchondroses may be physiologically intense and sometimes asymmetric, careful evaluation of these regions with adjunct blood pool and delayed SPECT imaging is suggested.

Spine

Spine lesions are seen in ∼ 25–30% of patients, with predilection for thoracic vertebrae [5,7,8]. Radiographic appearance of spinal CRMO varies; however, the most common feature is irregularities of a vertebral endplate with adjacent sclerosis, resembling sequelae of spondylodiskitis. There may be solitary or multiple vertebral involvement, usually with a noncontiguous pattern. The adjacent disk may sometimes be involved, but the intervertebral space is maintained, distinguishing CRMO from infectious spondylodiskitis [28]. Pathologic compression fractures of vertebral bodies are not uncommon and may result in vertebra plana. Although bone scintigraphy is more sensitive than plain radiography, vertebral lesions may be difficult to visualize with planar bone scintigraphy, especially when vertebra plana occurs. SPECT imaging enhances the sensitivity of bone scintigraphy (Fig. 4).

Mandible

CRMO of the mandible is well described. The imaging appearance of mandibular CRMO is similar to that at other sites of disease [22,33] (Fig. 5). In a recent pediatric cohort of 70 patients, mandibular involvement was seen in 21% of patients. Although mandibular disease can either be isolated or accompanied by disease at other sites, the mandible was the most commonly affected bone in patients with unifocal disease in this cohort, seen in 12 of 20 patients with unifocal disease [7].

Clavicle

Clavicle involvement of CRMO is common and may be seen in ∼ 25% of patients [4,7]. Clavicular lesions typically start at the medial end, with sparing of the sternoclavicular joint [8,14,28,29] (Fig. 6). Among children and adolescents, CRMO is the most common nontumoral disease involving the clavicle. Conversely, acute hematogenous osteomyelitis of the clavicle is extremely rare. Clavicular CRMO lesions may have the aggressive appearance of a primary bone malignancy with extension of inflammatory changes to the surrounding soft tissues. CRMO lesions of the clavicle may persist for several years and can cause complications, such as thoracic outlet syndrome [14,22].

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Fig. 1

Bilateral symmetric CRMO of tubular bones in a 13-year-old girl who presented with left knee pain. (a) AP radiograph of the left knee showing a poorly marginated mixed lucent and sclerotic lesion with surrounding periosteal reaction in the left femoral metaphysis (arrow). (b) Coronal FS T2-weighted MR image of the bilateral femurs showing extensively high bone marrow signal in the left femoral metaphysis with surrounding soft-tissue edema and a less conspicuous lesion in the right femoral metaphysis. (c) Anterior blood pool and (d) delayed images of bone scintigraphy showing bilateral metaphyseal and left diaphyseal increased activity. The diagnosis of CRMO was confirmed through histopathologic analysis and negative culture results from bone biopsy. AP, anteroposterior; CRMO, chronic recurrent multifocal osteomyelitis; FS, fat suppressed.

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Fig. 2

Bilateral distal tibial involvement in an 11-year-old girl, who complained of migratory bone and joint pain with fever. (a) Anterior blood pool and (b) delayed-phase images of the ankles showing increased activity at the distal metaphysis and physis of the left tibia and fibula (arrows). There is also less apparent increased activity in the contralateral distal tibial metaphysis (dotted arrows). (c, d) Sagittal FS T1-weighted postcontrast MR images showing bilateral, patchy enhancement in the bilateral distal tibial metadiaphyses, greater on the left. The left fibular metaphysis was similarly involved; not shown. FS, fat suppressed.

Other sites

CRMO of small bones appears to be uncommon. However, this may be due to limitations of imaging techniques, especially when lesions are asymptomatic. Foot lesions may be underestimated because of the difficulty in differentiating stress reaction, bone contusion, or other trauma from CRMO lesions on both bone

scintigraphy and MRI. Radiography is insensitive for detecting lesions in the foot. Because of their small size, hand lesions are difficult to detect with whole-body imaging techniques if dedicated hand images are not obtained. Among the small bones, CRMO is more common in the feet than in the hands. Calcaneal involvement can be seen in up to 19% of patients [4].

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Fig. 3

A 9-year-old girl with a history of right hip pain and limp for 2 months. (a) AP radiograph of the pelvis showing destructive changes involving the right pubic symphysis with periosteal reaction along the superior pubic ramus (arrowhead). (b) Selected coronal STIR image of a pelvic MRI showing extensively high signal in the right superior pubic ramus and surrounding soft tissues. (c) Blood pool and (d) delayed-phase images showing increased activity in the right superior and inferior pubic rami, left acetabulum, and the right sacrum (arrows). Biopsy of the lesion in the right pubic symphysis was compatible with chronic osteomyelitis, and microbiologic test results were negative. AP, anteroposterior; STIR, short tau inversion recovery.

Differential diagnosis

The diagnosis of CRMO is often challenging and can be delayed as several diseases can present with similar clinical courses and imaging findings. The differential diagnosis of CRMO includes infectious osteomyelitis, neoplasm, bone trauma, osteonecrosis, and juvenile idiopathic arthritis. An infectious etiology is usually considered first in young children presenting with bone pain. Infants and children

with acute hematogenous osteomyelitis may present with multiple bone involvement, sometimes with symmetrical distribution resembling that in CRMO. Malignancy should be excluded, particularly in patients with solitary lesions. The main malignancies to be considered include lymphoma, leukemia, neuroblastoma, and Ewing’s sarcoma. Other bone lesions, such as fibrous dysplasia, histiocytosis, osteoid osteoma, and osteoma, may overlap in appearance.

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Fig. 4

A 13-year-old girl with a history of CRMO, right knee pain, recent-onset back pain, and known right distal femur lesion. (a) Coronal T1-FS postcontrast MR images of the right knee showing marrow enhancement in the distal femoral metaphysis, crossing the physis into the epiphysis with associated focal irregularity of the physis. (b, c) Whole-body bone scintigraphy images at soft-tissue and delayed phases showing asymmetric activity of the knees with juxtaphyseal increased activity in the right lateral distal femur (arrows), corresponding to the MRI. There is also increased activity with widened appearance of the growth plate in the left proximal tibia (arrows). The whole-body delayed image suggests foci increased activity corresponding to the upper costovertebral junctions (dotted arrows). (d) An MIP image of bone SPECT showing better delineation of areas of increased activity at several costovertebral junctions, suggesting involvement of CRMO. (e) Subsequently obtained AP radiograph of the upper thoracic spine showing subtle sclerosis involving the left second and third, and possibly the right fifth, costovertebral junctions (dotted arrows), corresponding to bone scintigraphy. Because the left knee was asymptomatic, it was further evaluated with MRI. (f) Selected coronal STIR image of the tibiae from a whole-body MRI image showing abnormal signal within the proximal metaphysis of the left tibia extending across the growth plate into the left proximal tibial epiphysis (arrowhead), corresponding to bone scintigraphy. AP, anteroposterior; CRMO, chronic recurrent multifocal osteomyelitis; FS, fat suppressed; MIP, maximum intensity projection; SPECT, single-photon emission computed tomography; STIR, short tau inversion recovery.

Discussion Musculoskeletal pain is common among children and adolescents. Approximately 20% of preteens and early adolescents experience new-onset, nontraumatic musculoskeletal pain over a 1-year period [34]. Although the true incidence of CRMO is not known among these children, it is probably underdiagnosed because of the

absence of specific diagnostic tests and criteria and lack of awareness of clinicians, imaging specialists, and pathologists. It is important to diagnose CRMO to provide optimal clinical care and reduce the incidence of complications. The following common clinical and imaging features of CRMO may allow the imaging specialist to suggest the correct diagnosis:

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Fig. 5

A 9-year-old boy with a history of progressive left-sided jaw pain and swelling for 10 days. He also complained of left foot and thigh pain. (a, b) Axial CT of the mandible, shown with bone and soft-tissue windows, showing an expansile, lytic lesion of the left mandible with surrounding soft-tissue swelling (arrows), which indicates osteomyelitis. (c, d) Bone scintigraphy image showing prominent hyperemia and increased osseous activity in the left mandible, corresponding to CT. There is also increased activity of the left inferior pubic ramus, left ischium, and left calcaneus (dotted arrows). The lateral aspect of the distal left femoral growth plate appears to be widened with juxtaphyseal increased activity (dotted arrow). CT, computed tomography.

(1) Prolonged course with recurrent episodes. (2) Involvement of multiple sites, especially the lower extremities. (3) Predilection for metaphyses/juxtaphyses. (4) Symmetric lesions.

(5) Involvement of locations that are uncommon for hematogenous osteomyelitis, such as the clavicle. (6) No abscess, fistula, or sequestra on anatomic imaging. (7) Signs of subacute or chronic osteomyelitis with negative bone/tissue cultures.

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Fig. 6

A 12-year-old girl with a history of right clavicular lesion. (a) Axial CT image of the clavicles showing an expansile lytic lesion involving the medial aspect of the right clavicle (arrowhead). (b) Coronal STIR MR image showing patchy increased marrow signal and periosteal reaction (arrow). Bone scintigraphy was performed to evaluate for synchronous lesions. (c, d) Blood pool and delayed-phase images of the whole body showing increased activity in the right medial clavicle. There is also increased activity in the left distal tibial juxtaphyseal and metaphyseal regions. Subtle increased activity is seen at the lateral juxtaphyseal region of the distal right femur as well (arrows). (e) A follow-up oblique radiograph of the left ankle taken 1 day later, showing an ill-defined lucent lesion in the distal tibial metaphysis, adjacent to the growth plate (arrow). Biopsy of the clavicle showed active chronic osteomyelitis with granulomatous changes without growth on bacterial culture, consistent with the diagnosis of CRMO. CRMO, chronic recurrent multifocal osteomyelitis; CT, computed tomography; STIR, short tau inversion recovery.

(8) Association with autoinflammatory disorders such as psoriasis, inflammatory bowel disease, or palmoplantar pustulosis. (9) Improvement with NSAIDs but lack of response to antibiotic treatment. The findings on bone scintigraphy are not entirely specific to CRMO. This is also true for other imaging modalities, including MRI. Nonetheless, CRMO can be confidently diagnosed with the recognition of typical imaging patterns in the appropriate clinical setting. The large variety of locations and multifocality of this disease highlight the necessity to completely include the whole skeleton in blood pool imaging and delayed-phase bone scintigraphy.

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Acknowledgements Conflicts of interest

There are no conflicts of interest.

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Chronic recurrent multifocal osteomyelitis: typical patterns of bone involvement in whole-body bone scintigraphy.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease of unknown etiology. It affects children and adolescents predomi...
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