Journal of Medical Imaging and Radiation Oncology •• (2015) ••–••
RADIOLO GY—O R I G I N A L A RT I C L E
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Chronic recurrent multifocal osteomyelitis: A rare entity Gajan Surendra and Umesh Shetty Medical Imaging Department, Mater Children’s Hospital, South Brisbane, Queensland, Australia
G Surendra MBBS; U Shetty MBBS, MD, DNB, FRANZCR.
Abstract
Submitted 16 December 2014; accepted 27 February 2015.
Introduction: Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease which is characterised by non-infectious bone lesions at multiple sites which have a relapsing nature. Our aim is to examine the role of radiology in diagnosis and management of CRMO patients who have been managed at the Mater Children’s Hospital. Methods: This is a retrospective analysis of patients who have been managed with CRMO at the Mater Hospital since 2002. Inclusion criteria included a final diagnosis of CRMO. Exclusion criteria were a diagnosis more likely than CRMO. Medical images for each patient were evaluated for lesion features, location of lesion, number of bony lesions and whether or not the radiographic appearance would be characteristic of CRMO. Results: Initially, 17 patients were included in the study; however, seven patients were excluded due to a more likely alternative diagnosis. In total, 24 lesions were detected; the most common anatomical sites were the spine (25%), feet (25%), ribs (16.7%) and femur (12.5%). Plain radiography lacked sensitivity, but it was important in initial screening and evaluating progress of lesions. MRI is important for targeted investigation and further evaluation of lesions. Bone scintigraphy is useful for detecting other affected sites. Due to the exposure to radiation, computed tomography is generally avoided. Conclusions: The combination of imaging modalities plays a large role in CRMO diagnosis. CRMO lesions usually appear ill defined with no pathognomonic features. The distribution of bony lesions can aid diagnosis, with lower limbs and clavicles commonly affected.
doi:10.1111/1754-9485.12311
Key words: chronic nonbacterial osteomyelitis; chronic recurrent multifocal osteomyelitis; CRMO.
Correspondence Dr Gajan Surendra, Medical Imaging Department, Mater Children’s Hospital, Raymond Terrace, South Brisbane, Qld 4101, Australia. Email: [email protected] Conflict of interest: The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Introduction Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory disease which affects children, adolescents and seldom adults.1 The pathogenesis is poorly understood, but the disease is characterised by non-infectious bone lesions at multiple sites which have a relapsing nature.2 There has been a reported association with other auto-inflammatory disorders.3 There is very little data on the incidence of CRMO; however, it has been estimated to affect 1:1000000 people,4 but due to the difficulties with diagnosis, the number of cases is likely under estimated. Diagnosis of CRMO relies on a combination of radiological imaging, clinical examination, laboratory investigations and multidisciplinary team review. There are no pathognomonic features and thus remains a diagnosis of exclusion.5
© 2015 The Royal Australian and New Zealand College of Radiologists
Difficulties with diagnosis also arise due to varied clinical presentation. Usually, patients will present with pain, tenderness, swelling and decreased range of motion of a single site. Typically, CRMO has an insidious onset so exact time of disease onset may be unclear.5 Initial erythrocyte sedimentation rate, C-reactive protein and white cell count may be within normal limits. Bone biopsy reveals non-specific inflammatory changes with leukocyte infiltration. There is a reported association between CRMO and other auto-inflammatory conditions including psoriasis, inflammatory bowel disease and Wegener’s granulomatosis.3 Radiological evaluation of CRMO usually begins with plain radiographs of the symptomatic site which may demonstrate an osteolytic or sclerotic lesion. Follow-up MRI may demonstrate associated marrow oedema, periostitis, soft tissue inflammation and transphyseal disease.6 Common sites of bony lesions are tubular long
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bones, in particular the metaphysis adjacent to the growth plate, clavicle, mandible, spine, pelvis, ribs, sternum and bones of the hands and feet.1 The tibia is the most commonly affected bone. Whole body MR imaging or bone scan can be performed to determine other sites of skeletal involvement.5,6 This current project endeavours to examine the role of radiology in the diagnosis and management of patients who have had CRMO managed at the Mater Children’s Hospital over the past 12 years.
Methods As per the National Statement, this project was defined as an Audit of Practice against Current Standards. Ethics approval was obtained from the Mater Research Ethics Committee. Informed consent was not required. A cohort of patients was selected retrospectively. Mater Hospital electronic records were searched for the terms ‘CRMO’ and ‘chronic recurrent multifocal osteomyelitis’. The search extended as far back as 2002. Initially, 17 patients were included in the study. However, seven patients were subsequently excluded because of a more likely alternative diagnosis. Of these patients, three patients had acute osteomyelitis, two patients had Q-fever osteomyelitis, one patient had non-accidental injury and one patient had juvenile arthritis. All patients were managed at the Mater Children’s Hospital; however, their initial presentation may have been at an external site. Imaging was performed at various centres, and they included plain radiographs, MRI, CT and bone scintigraphy. Acute and follow-up imaging were analysed by a paediatric radiologist with 20 years of experience in general and paediatric radiology. Images were evaluated for lesion features, location of lesion, number of bony lesions and whether or not the radiographic appearance would be characteristic of CRMO. This was then crossmatched with the original imaging reports.
A lesion was said to be positive on plain radiograph if it was said to be osteolytic, osteolytic with surrounding sclerosis or predominately sclerotic with associated hyperosteosis. In the ribs, however, evidence of rib destruction with periosteal reaction or irregularity of rib contour was deemed a positive result. A positive lesion on MRI was regarded as findings of marrow oedema appearing hypointense on T1-weightbased imaging and hyperintense on T2-weight-based imaging. Positive spinal lesions were required to demonstrate altered signal intensity of vertebral marrow, which may or may not have been accompanied by loss of vertebral height. Bone scans were three-phase studies with dynamic, blood pool and delayed images and were performed with technetium-99m. Lesions were recorded as positive on bone scan if abnormal increased uptake was noted and correlated imaging did not demonstrate fractures or arthropathies. A positive lesion on computed tomography was defined as a lytic area with surrounding sclerosis and hyperostosis. Vertebral lesions were required to demonstrate bone erosion or destruction but did not necessarily require loss of vertebral height. Clinical and laboratory data were accessed from patient records. All data were then compared and contrasted to current literature.
Results Initially, 17 patients were included; however, seven of these patients were considered to have a more likely alternative diagnosis so were subsequently excluded from the study. Of the remaining patient population, there were five males and five females. All patients presented with a single symptomatic site. The median age of symptom onset was 8 years and 1 month (interquartile range of 5 years to 11 years and 10 months) (Table 1). There was a median of 3 months from symptom onset to diagnosis (interquartile range 1.5–6.5 months). Seven
Table 1. Patient demographics Gender
Clinical presentation
Age of symptom onset
Time to diagnosis
Biopsy
Site of disease
M F F M M
Left knee pain Right knee pain Right heel pain Back pain Back pain
5 years, 0 months 12 years, 5 months 1 year, 6 months 11 years, 1 month 8 years, 10 months
1 month 5 months 1 month 12 months 13 months
Yes Yes Yes Yes Yes
F
Right foot pain
7 years, 3 months
7 months
No
M F M F
Right clavicle pain Lower back pain Right toe pain Left knee pain
11 years, 10 months 14 years, 6 months 9 years, 4 months 2 years, 1 month
1 month 3 months 3 months 3 months
No Yes No Yes
L) lateral femoral condyle R) distal femur, Left 6th rib, L1 spine R) heel, L) scapula L1 vertebra T7 and T11 vertebra, L) tibia, L) femur, R) 4th rib, R) 10th rib, L) 5th rib R) 4th metatarsal, R) 2nd metatarsal, R) cuboid, S1 vertebra, Mandible R) clavicle L2 vertebra R) 5th metatarsal, R) cuboid L) tibia
2
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Table 2. Lesion locations and the sensitivities of various imaging modalities Plain film
Long bones Tibia Fibula Femur Radius Ulna Mandible Spine Clavicle Scapula Others Hands Feet Ribs Total lesions
MRI
Bone scan
CT scan
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
2 0 3 0 0 1 6 1 1
2 0 3 0 0 1 5 1 1
2 0 3 0 0 0 4 1 0
1 0 2 0 0 1 5 1 1
1 0 2 0 0 1 5 1 1
1 0 3 0 0 1 6 1 1
1 0 2 0 0 1 6 1 1
0 0 0 0 0 0 4 1 0
0 0 0 0 0 0 4 1 0
0 6 4 24
0 6 4 23
0 3 2 15
0 6 1 18
0 6 1 18
0 4 4 21
0 4 4 20
0 0 0 5
0 0 0 5
out of 10 patients were biopsied, and all were culture negative while histopathology demonstrated changes consistent with chronic inflammation. Only four patients presented with either an elevated ESR (>30) or CRP (>5). Five patients demonstrated unifocal disease, one patient demonstrated unilateral multifocal disease and four patients demonstrated bilateral multifocal disease. Twenty-four lesions were detected (median of 1.5 lesions per patient, interquartile range of 1–2.75 lesions) (Table 2). The most frequent anatomical site affected was the spine (25%), the feet (25%), ribs (16.7%) and the femur (12.5%). No lesions were found in the cranium, fibula, sternum, pelvis or the upper limbs. Plain radiography demonstrated 15 lesions out of the 23 that were imaged. Plain radiography depicted all lesions in the lower limbs and clavicle but lacked sensitivity in all other anatomical areas. MRI detected 18 out of 18 bony lesions imaged. Eight patients underwent bone scintigraphy, and 20 out of 21 lesions were detected. Bone scintigraphy failed to detect a femoral lesion. This lesion was demonstrated in plain radiograph and MRI. CT demonstrated five out of five lesions imaged.
Discussion There is no gold standard imaging modality for CRMO lesions; however, it is evident that the combination of various imaging modalities plays a large role in disease diagnosis and management. Our audit demonstrates that the approach to imaging when evaluating bony lesions generally begins with plain radiography. If a symptomatic site demonstrates no bony lesion on plain radiography, evaluation with MR imaging is indicated. MR imaging can also be utilised to define detected lesions. Once a diag-
© 2015 The Royal Australian and New Zealand College of Radiologists
nosis of CRMO is suspected or established, then distant asymptomatic sites can be located using whole body MRI or bone scintigraphy.1 The literature suggests that whole body MR imaging may be superior to bone scintigraphy. MR imaging provides greater anatomical and morphological detail, and with bone scintigraphy, there is an element of normal radionucleotide uptake in metaphyseal regions of tubular long bones.3 In our analysis, only one patient had whole body MR, whereas eight patients had bone scintigraphy. In practice, bone scintigraphy is preferred as it is cheaper and easily obtained when compared with whole body MR imaging. Computed tomography is generally avoided due to radiation risk; however, it is often preferred in cases of vertebral osteomyelitis.7 Our audit demonstrates that in practice, CT is generally reserved for spinal lesions in the paediatric population. Detected lesions had varied appearance but generally appeared ill defined. Plain radiograph demonstrated osteolytic, osteosclerotic or sclerotic lesions. MRI demonstrated oedema-like lesions that were hypointense on T1-weight-based imaging and hyperintense on T2-weight-based imaging. Bone scan demonstrated nonspecific increased tracer uptake. Computed tomography demonstrated lesions that were lytic with surrounding sclerosis and possible hyperostosis. There were no pathognomonic features. This audit demonstrates CRMO manifests both as unifocal and multifocal disease, as well as unilateral and bilateral. Patients with CRMO have been described to most often present between 9 and 14 years of age, and our audit demonstrated a median age of 8 years and 1 month. Several studies have shown a female predisposition with a ratio of 1:2.1; however, our study shows a ratio of 1:1 male to female.1
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The lower extremities are reported to be the most affected sites. In a study by Fritz et al., 21% of lesions were located in the distal femur and 17% of lesions in the proximal tibia.2 Our study demonstrated similar results to these studies, with the lower extremity being most commonly affected (46%), made up of femur (12.5%), tibia (8%) and bones of the feet (25%). Long bone metaphyseal lesions were far more common than epiphyseal lesions. The upper extremity only made up 8% of total lesions. Lesions were only found in the scapula (4%) and clavicle (4%). The clavicle has been reported to be affected in up to 5% of cases.5 Spinal lesions are much less common, and an analysis by Jurrians et al. suggested they account for only 3% of lesions.8 In our population, spinal lesions accounted for 25% of total lesions. Mandibular lesions made up 4% of total lesions in our study which is in keeping with the literature where it is reported to be 5%.1 In our study, plain radiography had a sensitivity of 65%. In the literature, radiography has been demonstrated to have a sensitivity between 43% and 75%. Computed tomography has been shown to have a 67% sensitivity with regard to chronic osteomyelitis.7 CT demonstrated 100% sensitivity in our study. However, it is worth noting that only five lesions were imaged with CT and that all of these lesions were also demonstrated by bone scan and MRI. There were a few points of interest in this audit. Bone scintigraphy failed to detect one lesion which was located on the medial aspect of the lateral femoral condyle. Plain radiography demonstrated a lucent area surrounded by sclerosis, and MRI demonstrated an osseous abscess with associated oedema. This suggests that further imaging is warranted in symptomatic sites despite no apparent lesion on bone scintigraphy. One patient had a left knee epiphyseal lesion with an associated effusion on MR. These features were more suggestive of an infectious aetiology; however, this patient underwent a biopsy which demonstrated no infectious cause. A major limitation of our study is sample size. Our population only consisted of 10 patients, so it is difficult to apply our findings in the broader sense. However, the
4
literature on CRMO is scarce, and our primary aim was to contribute to the limited pool of available data. Data quality also proved an issue as CRMO is difficult to diagnose. SAPHO Syndrome and Majeed Syndrome are different disease processes that are clinically very similar to CRMO.3 Misdiagnosis is relatively common, and thus, these patients would not have been included in our study. Finally, as there is no gold standard for imaging these lesions, it is difficult to ascertain whether a lesion detected by one imaging modality but not detected by another implies a false positive or a false negative result, especially at asymptomatic sites.
Conclusions Our audit demonstrates that the combination of imaging modalities plays a large role in CRMO diagnosis and management. Although plain radiography lacks sensitivity, it is important in initial evaluation. Additionally, plain radiography is a cheap and effective method to assess progress of the disease over time.5 MR imaging is important for further evaluation of known bone lesions and for further investigation into symptomatic sites. Bone scintigraphy is useful for detecting distal sites of disease involvement. Whole body MR is also useful in detecting distal sites; however, at this juncture, it seems to be less practical than bone scintigraphy. Both MR imaging and bone scintigraphy demonstrate high sensitivity. Computed tomography also has a high sensitivity, but due to radiation exposure, it is mostly reserved for spinal lesions.9 CRMO lesions usually appear ill-defined with no pathognomonic features. The distribution of bony lesions can aid diagnosis, with lower limbs and spinal lesions being common and upper limbs lesions being uncommon. Metaphyseal involvement is much more common than epiphyseal involvement.2 Features consistent with these findings should arouse a high index of suspicion for CRMO. Due to the low incidence and difficulty with diagnosis, current data on CRMO are sparse, and further study is warranted. Increasing awareness of this disease entity would improve data quality.
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Case 1 11-year-old male presents with right clavicular pain
(a) Plain x-ray showing expanded medial to mid third right clavicle with sclerosis. (b) T2W fat-saturated coronal image showing high-signal oedema within the medial clavicle which extends to the sternoclavicular joint. Associated irregular cortical erosion and expansion of the head of the clavicle. (c) Whole body bone scan showing increased tracer uptake in the medial right clavicle. No other focal lesions detected.
© 2015 The Royal Australian and New Zealand College of Radiologists
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Case 2 11-year-old male presents with lower back pain
(a) Initial CT scan demonstrating bone destruction of the anterosuperior aspect of the L1 vertebral body with anterior wedging. Irregular erosion (Schmorl’s node) of inferior end-plate of T12 also noted. (b) Plain x-ray at 1 year showing anterior wedging of T11 and L1 vertebrae with 30% height reduction. Minimal anterior wedging of T9 and T10 vertebrae is also seen. (c) T2W MRI spine at 2 years showing severe anterior wedging of the T11 and L1 vertebral bodies with marked irregularity and depression of the superior endplates. Note: Biopsy of the L1 vertebrae was culture negative and showed changes of chronic inflammation.
6
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Case 3 7-year-old female presents with right foot pain
(a) Plain x-ray right foot demonstrating minimal sclerosis second and fourth metatarsals. Initially thought to be post traumatic. (b) STIR MRI images showing multifocal bone lesions in the second and fourth metatarsals, talus and cuboid. (c) Bone scintigraphy showing multiple sites of tracer uptake in both blood pool and delayed images. These sites included second and fourth metatarsals, calcaneum, S1, and the left mandible.
© 2015 The Royal Australian and New Zealand College of Radiologists
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Case 4 18–month-old female with right heel pain
8
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
(a) Plain x-ray demonstrating 5-mm rounded radiolucent focus within the posterior body of the os calcis with associated cortical thinning. (b) Bone scintigraphy showing tracer uptake in the right calcaneum and an additional focus in the left scapula. (c) Whole body coronal STIR and dedicated T2W post-contrast images showing high signal intensity lesions within the right os calcis and left body of scapula. Note: Biopsy of the calcaneum did not reveal active infection or neoplasia.
References 1. Khanna G, Takashi S, Ferguson P. Imaging of chronic recurrent multifocal osteomyelitis. Radiographics 2009; 29: 1159–77. 2. Fritz J, Tzaribatchev N, Claussen C, Carrino J, Horger M. Chronic recurrent multifocal osteomyelitis: comparison of whole-body MR imaging with radiography and correlation with clinical and laboratory data. Radiology 2009; 252: 842–51. 3. Ferguson P, Sandu M. Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis. Curr Rheumatol Rep 2012; 14: 130–41. 4. Sozeri B, Yildiz B, Sezak M, Argin M. Clinical experiences in patients with chronic recurrent multifocal osteomyelitis. Pediatr Rheumatol Online J 2013; 11: 196. 5. Mandell G, Contreras S, Conard K, Harcke H, Maas K. Bone scintigraphy in the detection of chronic recurrent
© 2015 The Royal Australian and New Zealand College of Radiologists
6.
7.
8.
9.
multifocal osteomyelitis. J Nucl Med 1998; 39: 1778–83. Chavhan G, Babyn P. Whole-body MR imaging in children: principles, technique, current applications, and future directions. Radiographics 2011; 31: 1757–72. Pineda C, Espinosa R, Pena A. Radiographic imaging in osteomyelitis: the role of plain radiography, computed tomography, ultrasonography, magnetic resonance Imaging, and scintigraphy. Semin Plast Surg 2009; 23: 80–9. Jurrians E, Singh N, Finlay K, Friedman L. Imaging of chronic recurrent multifocial osteomyelitis. Radiol Clin North Am 2001; 39: 305–27. Dipoce J, Jbara M, Brenner A. Pediatric osteomyelitis: a scintigraphic case-based review. Radiographics 2012; 32: 865–78.
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RADIOLO GY—O R I G I N A L A RT I C L E
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Chronic recurrent multifocal osteomyelitis: A rare entity Gajan Surendra and Umesh Shetty Medical Imaging Department, Mater Children’s Hospital, South Brisbane, Queensland, Australia
G Surendra MBBS; U Shetty MBBS, MD, DNB, FRANZCR.
Abstract
Submitted 16 December 2014; accepted 27 February 2015.
Introduction: Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease which is characterised by non-infectious bone lesions at multiple sites which have a relapsing nature. Our aim is to examine the role of radiology in diagnosis and management of CRMO patients who have been managed at the Mater Children’s Hospital. Methods: This is a retrospective analysis of patients who have been managed with CRMO at the Mater Hospital since 2002. Inclusion criteria included a final diagnosis of CRMO. Exclusion criteria were a diagnosis more likely than CRMO. Medical images for each patient were evaluated for lesion features, location of lesion, number of bony lesions and whether or not the radiographic appearance would be characteristic of CRMO. Results: Initially, 17 patients were included in the study; however, seven patients were excluded due to a more likely alternative diagnosis. In total, 24 lesions were detected; the most common anatomical sites were the spine (25%), feet (25%), ribs (16.7%) and femur (12.5%). Plain radiography lacked sensitivity, but it was important in initial screening and evaluating progress of lesions. MRI is important for targeted investigation and further evaluation of lesions. Bone scintigraphy is useful for detecting other affected sites. Due to the exposure to radiation, computed tomography is generally avoided. Conclusions: The combination of imaging modalities plays a large role in CRMO diagnosis. CRMO lesions usually appear ill defined with no pathognomonic features. The distribution of bony lesions can aid diagnosis, with lower limbs and clavicles commonly affected.
doi:10.1111/1754-9485.12311
Key words: chronic nonbacterial osteomyelitis; chronic recurrent multifocal osteomyelitis; CRMO.
Correspondence Dr Gajan Surendra, Medical Imaging Department, Mater Children’s Hospital, Raymond Terrace, South Brisbane, Qld 4101, Australia. Email: [email protected] Conflict of interest: The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
Introduction Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory disease which affects children, adolescents and seldom adults.1 The pathogenesis is poorly understood, but the disease is characterised by non-infectious bone lesions at multiple sites which have a relapsing nature.2 There has been a reported association with other auto-inflammatory disorders.3 There is very little data on the incidence of CRMO; however, it has been estimated to affect 1:1000000 people,4 but due to the difficulties with diagnosis, the number of cases is likely under estimated. Diagnosis of CRMO relies on a combination of radiological imaging, clinical examination, laboratory investigations and multidisciplinary team review. There are no pathognomonic features and thus remains a diagnosis of exclusion.5
© 2015 The Royal Australian and New Zealand College of Radiologists
Difficulties with diagnosis also arise due to varied clinical presentation. Usually, patients will present with pain, tenderness, swelling and decreased range of motion of a single site. Typically, CRMO has an insidious onset so exact time of disease onset may be unclear.5 Initial erythrocyte sedimentation rate, C-reactive protein and white cell count may be within normal limits. Bone biopsy reveals non-specific inflammatory changes with leukocyte infiltration. There is a reported association between CRMO and other auto-inflammatory conditions including psoriasis, inflammatory bowel disease and Wegener’s granulomatosis.3 Radiological evaluation of CRMO usually begins with plain radiographs of the symptomatic site which may demonstrate an osteolytic or sclerotic lesion. Follow-up MRI may demonstrate associated marrow oedema, periostitis, soft tissue inflammation and transphyseal disease.6 Common sites of bony lesions are tubular long
1
G Surendra and U Shetty
bones, in particular the metaphysis adjacent to the growth plate, clavicle, mandible, spine, pelvis, ribs, sternum and bones of the hands and feet.1 The tibia is the most commonly affected bone. Whole body MR imaging or bone scan can be performed to determine other sites of skeletal involvement.5,6 This current project endeavours to examine the role of radiology in the diagnosis and management of patients who have had CRMO managed at the Mater Children’s Hospital over the past 12 years.
Methods As per the National Statement, this project was defined as an Audit of Practice against Current Standards. Ethics approval was obtained from the Mater Research Ethics Committee. Informed consent was not required. A cohort of patients was selected retrospectively. Mater Hospital electronic records were searched for the terms ‘CRMO’ and ‘chronic recurrent multifocal osteomyelitis’. The search extended as far back as 2002. Initially, 17 patients were included in the study. However, seven patients were subsequently excluded because of a more likely alternative diagnosis. Of these patients, three patients had acute osteomyelitis, two patients had Q-fever osteomyelitis, one patient had non-accidental injury and one patient had juvenile arthritis. All patients were managed at the Mater Children’s Hospital; however, their initial presentation may have been at an external site. Imaging was performed at various centres, and they included plain radiographs, MRI, CT and bone scintigraphy. Acute and follow-up imaging were analysed by a paediatric radiologist with 20 years of experience in general and paediatric radiology. Images were evaluated for lesion features, location of lesion, number of bony lesions and whether or not the radiographic appearance would be characteristic of CRMO. This was then crossmatched with the original imaging reports.
A lesion was said to be positive on plain radiograph if it was said to be osteolytic, osteolytic with surrounding sclerosis or predominately sclerotic with associated hyperosteosis. In the ribs, however, evidence of rib destruction with periosteal reaction or irregularity of rib contour was deemed a positive result. A positive lesion on MRI was regarded as findings of marrow oedema appearing hypointense on T1-weightbased imaging and hyperintense on T2-weight-based imaging. Positive spinal lesions were required to demonstrate altered signal intensity of vertebral marrow, which may or may not have been accompanied by loss of vertebral height. Bone scans were three-phase studies with dynamic, blood pool and delayed images and were performed with technetium-99m. Lesions were recorded as positive on bone scan if abnormal increased uptake was noted and correlated imaging did not demonstrate fractures or arthropathies. A positive lesion on computed tomography was defined as a lytic area with surrounding sclerosis and hyperostosis. Vertebral lesions were required to demonstrate bone erosion or destruction but did not necessarily require loss of vertebral height. Clinical and laboratory data were accessed from patient records. All data were then compared and contrasted to current literature.
Results Initially, 17 patients were included; however, seven of these patients were considered to have a more likely alternative diagnosis so were subsequently excluded from the study. Of the remaining patient population, there were five males and five females. All patients presented with a single symptomatic site. The median age of symptom onset was 8 years and 1 month (interquartile range of 5 years to 11 years and 10 months) (Table 1). There was a median of 3 months from symptom onset to diagnosis (interquartile range 1.5–6.5 months). Seven
Table 1. Patient demographics Gender
Clinical presentation
Age of symptom onset
Time to diagnosis
Biopsy
Site of disease
M F F M M
Left knee pain Right knee pain Right heel pain Back pain Back pain
5 years, 0 months 12 years, 5 months 1 year, 6 months 11 years, 1 month 8 years, 10 months
1 month 5 months 1 month 12 months 13 months
Yes Yes Yes Yes Yes
F
Right foot pain
7 years, 3 months
7 months
No
M F M F
Right clavicle pain Lower back pain Right toe pain Left knee pain
11 years, 10 months 14 years, 6 months 9 years, 4 months 2 years, 1 month
1 month 3 months 3 months 3 months
No Yes No Yes
L) lateral femoral condyle R) distal femur, Left 6th rib, L1 spine R) heel, L) scapula L1 vertebra T7 and T11 vertebra, L) tibia, L) femur, R) 4th rib, R) 10th rib, L) 5th rib R) 4th metatarsal, R) 2nd metatarsal, R) cuboid, S1 vertebra, Mandible R) clavicle L2 vertebra R) 5th metatarsal, R) cuboid L) tibia
2
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Table 2. Lesion locations and the sensitivities of various imaging modalities Plain film
Long bones Tibia Fibula Femur Radius Ulna Mandible Spine Clavicle Scapula Others Hands Feet Ribs Total lesions
MRI
Bone scan
CT scan
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
Lesions imaged
Lesions detected
2 0 3 0 0 1 6 1 1
2 0 3 0 0 1 5 1 1
2 0 3 0 0 0 4 1 0
1 0 2 0 0 1 5 1 1
1 0 2 0 0 1 5 1 1
1 0 3 0 0 1 6 1 1
1 0 2 0 0 1 6 1 1
0 0 0 0 0 0 4 1 0
0 0 0 0 0 0 4 1 0
0 6 4 24
0 6 4 23
0 3 2 15
0 6 1 18
0 6 1 18
0 4 4 21
0 4 4 20
0 0 0 5
0 0 0 5
out of 10 patients were biopsied, and all were culture negative while histopathology demonstrated changes consistent with chronic inflammation. Only four patients presented with either an elevated ESR (>30) or CRP (>5). Five patients demonstrated unifocal disease, one patient demonstrated unilateral multifocal disease and four patients demonstrated bilateral multifocal disease. Twenty-four lesions were detected (median of 1.5 lesions per patient, interquartile range of 1–2.75 lesions) (Table 2). The most frequent anatomical site affected was the spine (25%), the feet (25%), ribs (16.7%) and the femur (12.5%). No lesions were found in the cranium, fibula, sternum, pelvis or the upper limbs. Plain radiography demonstrated 15 lesions out of the 23 that were imaged. Plain radiography depicted all lesions in the lower limbs and clavicle but lacked sensitivity in all other anatomical areas. MRI detected 18 out of 18 bony lesions imaged. Eight patients underwent bone scintigraphy, and 20 out of 21 lesions were detected. Bone scintigraphy failed to detect a femoral lesion. This lesion was demonstrated in plain radiograph and MRI. CT demonstrated five out of five lesions imaged.
Discussion There is no gold standard imaging modality for CRMO lesions; however, it is evident that the combination of various imaging modalities plays a large role in disease diagnosis and management. Our audit demonstrates that the approach to imaging when evaluating bony lesions generally begins with plain radiography. If a symptomatic site demonstrates no bony lesion on plain radiography, evaluation with MR imaging is indicated. MR imaging can also be utilised to define detected lesions. Once a diag-
© 2015 The Royal Australian and New Zealand College of Radiologists
nosis of CRMO is suspected or established, then distant asymptomatic sites can be located using whole body MRI or bone scintigraphy.1 The literature suggests that whole body MR imaging may be superior to bone scintigraphy. MR imaging provides greater anatomical and morphological detail, and with bone scintigraphy, there is an element of normal radionucleotide uptake in metaphyseal regions of tubular long bones.3 In our analysis, only one patient had whole body MR, whereas eight patients had bone scintigraphy. In practice, bone scintigraphy is preferred as it is cheaper and easily obtained when compared with whole body MR imaging. Computed tomography is generally avoided due to radiation risk; however, it is often preferred in cases of vertebral osteomyelitis.7 Our audit demonstrates that in practice, CT is generally reserved for spinal lesions in the paediatric population. Detected lesions had varied appearance but generally appeared ill defined. Plain radiograph demonstrated osteolytic, osteosclerotic or sclerotic lesions. MRI demonstrated oedema-like lesions that were hypointense on T1-weight-based imaging and hyperintense on T2-weight-based imaging. Bone scan demonstrated nonspecific increased tracer uptake. Computed tomography demonstrated lesions that were lytic with surrounding sclerosis and possible hyperostosis. There were no pathognomonic features. This audit demonstrates CRMO manifests both as unifocal and multifocal disease, as well as unilateral and bilateral. Patients with CRMO have been described to most often present between 9 and 14 years of age, and our audit demonstrated a median age of 8 years and 1 month. Several studies have shown a female predisposition with a ratio of 1:2.1; however, our study shows a ratio of 1:1 male to female.1
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The lower extremities are reported to be the most affected sites. In a study by Fritz et al., 21% of lesions were located in the distal femur and 17% of lesions in the proximal tibia.2 Our study demonstrated similar results to these studies, with the lower extremity being most commonly affected (46%), made up of femur (12.5%), tibia (8%) and bones of the feet (25%). Long bone metaphyseal lesions were far more common than epiphyseal lesions. The upper extremity only made up 8% of total lesions. Lesions were only found in the scapula (4%) and clavicle (4%). The clavicle has been reported to be affected in up to 5% of cases.5 Spinal lesions are much less common, and an analysis by Jurrians et al. suggested they account for only 3% of lesions.8 In our population, spinal lesions accounted for 25% of total lesions. Mandibular lesions made up 4% of total lesions in our study which is in keeping with the literature where it is reported to be 5%.1 In our study, plain radiography had a sensitivity of 65%. In the literature, radiography has been demonstrated to have a sensitivity between 43% and 75%. Computed tomography has been shown to have a 67% sensitivity with regard to chronic osteomyelitis.7 CT demonstrated 100% sensitivity in our study. However, it is worth noting that only five lesions were imaged with CT and that all of these lesions were also demonstrated by bone scan and MRI. There were a few points of interest in this audit. Bone scintigraphy failed to detect one lesion which was located on the medial aspect of the lateral femoral condyle. Plain radiography demonstrated a lucent area surrounded by sclerosis, and MRI demonstrated an osseous abscess with associated oedema. This suggests that further imaging is warranted in symptomatic sites despite no apparent lesion on bone scintigraphy. One patient had a left knee epiphyseal lesion with an associated effusion on MR. These features were more suggestive of an infectious aetiology; however, this patient underwent a biopsy which demonstrated no infectious cause. A major limitation of our study is sample size. Our population only consisted of 10 patients, so it is difficult to apply our findings in the broader sense. However, the
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literature on CRMO is scarce, and our primary aim was to contribute to the limited pool of available data. Data quality also proved an issue as CRMO is difficult to diagnose. SAPHO Syndrome and Majeed Syndrome are different disease processes that are clinically very similar to CRMO.3 Misdiagnosis is relatively common, and thus, these patients would not have been included in our study. Finally, as there is no gold standard for imaging these lesions, it is difficult to ascertain whether a lesion detected by one imaging modality but not detected by another implies a false positive or a false negative result, especially at asymptomatic sites.
Conclusions Our audit demonstrates that the combination of imaging modalities plays a large role in CRMO diagnosis and management. Although plain radiography lacks sensitivity, it is important in initial evaluation. Additionally, plain radiography is a cheap and effective method to assess progress of the disease over time.5 MR imaging is important for further evaluation of known bone lesions and for further investigation into symptomatic sites. Bone scintigraphy is useful for detecting distal sites of disease involvement. Whole body MR is also useful in detecting distal sites; however, at this juncture, it seems to be less practical than bone scintigraphy. Both MR imaging and bone scintigraphy demonstrate high sensitivity. Computed tomography also has a high sensitivity, but due to radiation exposure, it is mostly reserved for spinal lesions.9 CRMO lesions usually appear ill-defined with no pathognomonic features. The distribution of bony lesions can aid diagnosis, with lower limbs and spinal lesions being common and upper limbs lesions being uncommon. Metaphyseal involvement is much more common than epiphyseal involvement.2 Features consistent with these findings should arouse a high index of suspicion for CRMO. Due to the low incidence and difficulty with diagnosis, current data on CRMO are sparse, and further study is warranted. Increasing awareness of this disease entity would improve data quality.
© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Case 1 11-year-old male presents with right clavicular pain
(a) Plain x-ray showing expanded medial to mid third right clavicle with sclerosis. (b) T2W fat-saturated coronal image showing high-signal oedema within the medial clavicle which extends to the sternoclavicular joint. Associated irregular cortical erosion and expansion of the head of the clavicle. (c) Whole body bone scan showing increased tracer uptake in the medial right clavicle. No other focal lesions detected.
© 2015 The Royal Australian and New Zealand College of Radiologists
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Case 2 11-year-old male presents with lower back pain
(a) Initial CT scan demonstrating bone destruction of the anterosuperior aspect of the L1 vertebral body with anterior wedging. Irregular erosion (Schmorl’s node) of inferior end-plate of T12 also noted. (b) Plain x-ray at 1 year showing anterior wedging of T11 and L1 vertebrae with 30% height reduction. Minimal anterior wedging of T9 and T10 vertebrae is also seen. (c) T2W MRI spine at 2 years showing severe anterior wedging of the T11 and L1 vertebral bodies with marked irregularity and depression of the superior endplates. Note: Biopsy of the L1 vertebrae was culture negative and showed changes of chronic inflammation.
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© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
Case 3 7-year-old female presents with right foot pain
(a) Plain x-ray right foot demonstrating minimal sclerosis second and fourth metatarsals. Initially thought to be post traumatic. (b) STIR MRI images showing multifocal bone lesions in the second and fourth metatarsals, talus and cuboid. (c) Bone scintigraphy showing multiple sites of tracer uptake in both blood pool and delayed images. These sites included second and fourth metatarsals, calcaneum, S1, and the left mandible.
© 2015 The Royal Australian and New Zealand College of Radiologists
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Case 4 18–month-old female with right heel pain
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© 2015 The Royal Australian and New Zealand College of Radiologists
CRMO: A rare entity
(a) Plain x-ray demonstrating 5-mm rounded radiolucent focus within the posterior body of the os calcis with associated cortical thinning. (b) Bone scintigraphy showing tracer uptake in the right calcaneum and an additional focus in the left scapula. (c) Whole body coronal STIR and dedicated T2W post-contrast images showing high signal intensity lesions within the right os calcis and left body of scapula. Note: Biopsy of the calcaneum did not reveal active infection or neoplasia.
References 1. Khanna G, Takashi S, Ferguson P. Imaging of chronic recurrent multifocal osteomyelitis. Radiographics 2009; 29: 1159–77. 2. Fritz J, Tzaribatchev N, Claussen C, Carrino J, Horger M. Chronic recurrent multifocal osteomyelitis: comparison of whole-body MR imaging with radiography and correlation with clinical and laboratory data. Radiology 2009; 252: 842–51. 3. Ferguson P, Sandu M. Current understanding of the pathogenesis and management of chronic recurrent multifocal osteomyelitis. Curr Rheumatol Rep 2012; 14: 130–41. 4. Sozeri B, Yildiz B, Sezak M, Argin M. Clinical experiences in patients with chronic recurrent multifocal osteomyelitis. Pediatr Rheumatol Online J 2013; 11: 196. 5. Mandell G, Contreras S, Conard K, Harcke H, Maas K. Bone scintigraphy in the detection of chronic recurrent
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multifocal osteomyelitis. J Nucl Med 1998; 39: 1778–83. Chavhan G, Babyn P. Whole-body MR imaging in children: principles, technique, current applications, and future directions. Radiographics 2011; 31: 1757–72. Pineda C, Espinosa R, Pena A. Radiographic imaging in osteomyelitis: the role of plain radiography, computed tomography, ultrasonography, magnetic resonance Imaging, and scintigraphy. Semin Plast Surg 2009; 23: 80–9. Jurrians E, Singh N, Finlay K, Friedman L. Imaging of chronic recurrent multifocial osteomyelitis. Radiol Clin North Am 2001; 39: 305–27. Dipoce J, Jbara M, Brenner A. Pediatric osteomyelitis: a scintigraphic case-based review. Radiographics 2012; 32: 865–78.
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