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Imaging of Chronic
Recurrent Multifocal
Geetika Khanna, MD, MS Takashi S. P. Sato, MD Polly Ferguson, MD
See www.rsna Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflam-
/rg_cme.html matory disorder of children and young adults that is characterized by
nonbacterial osteomyelitis. Patients typically present with multifocal
bone pain secondary to sterile osseous inflammation, and the disease
has a relapsing and remitting course. The cause of CRMO remains
After reading this
unclear, although the results of several studies have suggested a ge-
article and taking netic component. The typical imaging findings of CRMO include lytic
the test, the reader
will be able to:
and sclerotic lesions in the metaphyses of long bones and the medial
Discuss the epide- clavicles. Other common sites of disease are the vertebral bodies, pel-
miologic and clinical vis, ribs, and mandible. CRMO is often bilateral and multifocal at
features of chronic
recurrent multifocal presentation. Owing to the lack of a diagnostic test, CRMO remains
osteomyelitis. a diagnosis of exclusion. Although generally a self-limiting disease,
List the common CRMO can have a prolonged course and result in significant mor-
sites of disease in
chronic recurrent bidity. Radiologists can be the first to suggest this diagnosis given its
multifocal osteomy- characteristic radiographic appearance and distribution of disease.
Describe the typi-
Radiologists should be familiar with the typical imaging findings of
cal imaging findings CRMO to prevent unnecessary multiple biopsies and long-term anti-
of chronic recurrent
multifocal osteomy-
biotic treatment in children with CRMO.

Chronic recurrent multifocal osteomyelitis (CRMO) is an idiopathic inflammatory
TEACHING disorder of bone seen primarily in children and adolescents. The syndrome of CRMO
was originally described in 1972 in four children, under the name subacute and
See last page
chronic recurrent osteomyelitis (1). It is characterized by multifocal nonpyogenic
inflammatory bone lesions, a course of exacerbations and remissions, and an asso-
ciation with other inflammatory disorders (2). Since its original description, there
have been multiple case reports and studies of this disorder under a number of dif-
ferent names. These include subacute and chronic symmetric osteomyelitis, subacute

Abbreviations: CRMO = chronic recurrent multifocal osteomyelitis; SAPHO = synovitis, acne, pustulosis, hyperostosis, osteitis

RadioGraphics 2009; 29:11591177 Published online 10.1148/rg.294085244 Content Codes:

From the Mallinckrodt Institute of Radiology, Washington University School of Medicine, Campus Box 8131, St Louis, MO 63110 (G.K.); and the
Department of Pediatrics (P.F.), Carver College of Medicine (T.S.P.S.), University of Iowa, Iowa City, Iowa. Recipient of a Certificate of Merit award for
an education exhibit at the 2008 RSNA Annual Meeting. Received December 15, 2008; revision requested January 20, 2009, and received February 6;
accepted February 11. All authors have no financial relationships to disclose. Address correspondence to G.K. (e-mail:

RSNA, 2009

1160 July-August 2009

symmetric osteomyelitis, chronic multifocal sym- negative cultures in 23 of the 25 cases. Biopsy
metric osteomyelitis, chronic multifocal cleido- was not performed in two cases owing to a typical
metaphyseal osteomyelitis of childhood, and clinical picture and the presence of comorbid con-
chronic recurrent multifocal osteomyelitis (1,36). ditions (Crohn disease in one case and a pustular
The term CRMO was first used by Probst rash in the other), which supported the diagnosis
and colleagues (3,5) and encompasses the typical of CRMO. The images from these cases have been
clinical features of this entity: chronicity with a used to illustrate this pictorial review of CRMO.
protracted course, involvement of more than one
site, multiple exacerbations and relapses at old Epidemiologic Features
and new sites, and disease at sites that are typical CRMO is primarily a disease of childhood,
of osteomyelitis in children. Although primarily a with most patients presenting between 9 and 14
disease of children, it has been reported in older years of age. However, it has been described in
patients up to the age of 55 years (7,8). Since its infants as young as 6 months and in adults as
original description more than 3 decades ago, old as 55 years (7,911). Several studies have
several hundred cases of CRMO have been re- demonstrated a female predominance, with a
ported, likely owing to an increasing awareness male-to-female ratio of 1:2.1 (1215). Although
of this disease. Because CRMO is a diagnosis of most of the initial reports of CRMO came from
exclusion, it is likely that its actual prevalence is Europe, cases have been reported worldwide
higher than reported in the literature. (1,10,11,1619). The true prevalence of this
As imaging plays an important role in the condition remains unknown, with more than
evaluation of this disorder, it is important that 250 cases of CRMO reported in the literature
radiologists be familiar with its various manifesta- (12,13). Given the fact that it is a diagnosis of
tions. Suggestion of the diagnosis by a radiolo- exclusion, it is likely that the actual prevalence of
gist could help avoid unnecessary diagnostic CRMO is higher than realized.
procedures and antibiotic therapy and initiate an
appropriate therapy. In this article, we present Etiologic Factors
our clinical experience with CRMO and review The cause of CRMO remains elusive. Initial
its epidemiologic, etiologic, clinical, and histo- reports suggested an infectious origin, with sus-
pathologic features. We then describe the imag- pected organisms including Staphylococcus aureus,
ing approach, imaging appearances, and specific Mycoplasma hominis, Propionibacterium acnes, and
disease sites: tubular bones, clavicle, spine, pelvis, Chlamydia (7,9,20). However, larger studies have
mandible, and hands and feet. Finally, we discuss shown no common infectious agent responsible
differential diagnosis and outcomes and compare for CRMO (8,21). The coexistence of skin or-
CRMO with SAPHO (synovitis, acne, pustulosis, ganisms (such as diphtheroids and coagulase-
hyperostosis, osteitis) syndrome. negative staphylococci) in the biopsy cultures and
the failure of CRMO symptoms to improve with
Clinical Experience antibiotic therapy suggest that the organisms are
Between 2003 and 2008, 25 patients with CRMO likely contaminants of biopsy specimens (19,22).
were referred to the department of pediatric rheu- The association of CRMO with dermatologic
matology at our institution. There were 10 male disorders (such as psoriasis) and inflammatory
and 15 female patients with an average age at on- bowel disease and its response to steroids have
set of symptoms of 8.3 years (range, 2.524 years). led to the suggestion of an autoimmune cause
The three most common sites of disease at initial (2325). More recently, a genetic origin for
presentation were the lower extremities (39.7%), CRMO has been suggested secondary to obser-
spine (25.9%), and pelvis (20.7%). During the vation of disease in siblings and monozygotic
course of follow-up, a total of 121 bone lesions twins (10,11,2628). By means of a family-based
were seen in this patient population, with the association study, a susceptibility locus has been
most common site of disease being the lower ex- identified at 18q21.322 (29).
tremities (tibia, 15%; femur, 12%). Metaphyseal The genetic origin of CRMO is further sup-
lesions were the most common, accounting for ported by the identification of mutations of the
49% of all long bone lesions. LPIN2 gene in Majeed syndrome (10,11,30,31).
The diagnosis of CRMO in our patient popula- This rare autosomal-recessive syndrome is phe-
tion was confirmed by means of bone biopsy and notypically characterized by a triad of CRMO,
congenital dyserythropoietic anemia, and an in-
flammatory dermatosis. Spontaneously occurring
RG Volume 29 Number 4 Khanna et al 1161

Figures 1, 2. (1) CRMO in a 9-year-old girl with a history of mandibular pain and swelling. Techne-
tium 99m (99mTc) bone scan (anterior projection) shows increased uptake in the mandible. Bilaterally
symmetric radionuclide-avid lesions are present in the distal radius and ulna, distal femur, distal tibia,
and tarsal bones. Mild increased uptake is also seen in the proximal left tibial metaphysis and in the
maxilla. Bone biopsy and negative culture results led to a diagnosis of CRMO. (2) Chronic nonbacterial
osteomyelitis in a 14-year-old patient with a 3-year history of right arm pain. Radiograph (a) and sagit-
tal reformatted computed tomographic (CT) image (b) of the distal humerus show hyperostosis sec-
ondary to chronic periosteal reaction. There is marked cortical thickening with secondary compromise
of the medullary space. Specimens from two biopsies showed chronic inflammatory changes without
isolation of any organisms. A diagnosis of chronic nonbacterial osteomyelitis was established.

onset and vague nature of the symptoms. Labora-

tory findings at initial presentation are essentially
nonspecific, with the most common findings being
mildly elevated erythrocyte sedimentation rate and
mouse models of CRMO have been identified that C-reactive protein level with a normal white blood
show an autosomal-recessive gene defect local- cell count (26).
ized to the murine pstpip2 gene (27,32,33). Biopsy Although most patients present with a single
samples from these mice show histologic features symptomatic site, other sites of disease become
similar to those seen in CRMO (27,32,33). apparent at imaging or during clinical follow-
up (Fig 1). At any one time, the number of
Clinical Features osteomyelitis lesions can range from one to 18
Patients typically present with nonspecific com- (34,35). Although most patients with CRMO
plaints such as pain, tenderness, swelling, or lim- have recurrent and multifocal disease, a signifi-
ited range of motion at one or more sites. Systemic cant number of children with nonbacterial os-
manifestations such as fever, weight loss, and leth- teomyelitis may have only a single lesion, which
argy may be present but are unusual. The duration exhibits the same clinical, radiologic, and histo-
of symptoms can vary from days to several years logic features as multifocal disease (Fig 2). The
(19). In the series of Mandell et al (34), children term chronic nonbacterial osteomyelitis has been
were symptomatic for 3 days to 2 years before ini- suggested for this entity (21).
tial presentation. The duration of symptoms can
often be hard to assess because of the insidious
1162 July-August 2009

Pathologic Conditions Associated with CRMO

Dermatologic disorders
Palmoplantar pustulosis (16,37)
Psoriasis (23,37)
Acne fulminans (14)
Sweet syndrome (44)
Pyoderma gangrenosum (24,36,39)
Autoinflammatory disorders
Takayasu arteritis (24)
Wegener granulomatosis (41)
Gastrointestinal disorders
Crohn disease (25,38)
Ulcerative colitis (25)
Genetic syndromes
Majeed syndrome (10,11)
Other conditions
SAPHO syndrome (40)
Spondyloarthropathies (21,42,43)
Note.Numbers in parentheses are references.

CRMO has been reported in association

with skin lesions including palmoplantar pus-
tulosis, psoriasis vulgaris, Sweet syndrome, and
pyoderma gangrenosum (16,19,23,24,36,37)
(Table). In the review by Schultz et al (37), the
prevalence of cutaneous lesions in children with
CRMO was reported to be 25%, with pustulosis
being the most common, followed by psoriasis. Figure 3. CRMO in an 8-year-old boy with a 2-year
An association between CRMO and inflamma- history of multifocal bone pain in the lower extremi-
tory bowel disease, especially Crohn disease, has ties and pelvis. (a) Axial fat-saturated T2-weighted
also been reported (Fig 3) (25,37,38). magnetic resonance (MR) image shows scattered foci
of edema (black arrows) around the sacroiliac joints on
both sides. The edema is more extensive on the right
Histopathologic Findings side than on the left. The terminal ileum is thickened
Because the imaging findings of CRMO can (white arrow). (b) Spot fluoroscopic image shows the
be nonspecific, especially early in the course of thickened terminal ileum, a finding consistent with the
the disease or in the presence of a solitary le- patients history of Crohn disease.
sion, microbiologic and histopathologic analysis
are essential to exclude infectious osteomyelitis
and neoplastic lesions. At histologic evaluation, the histologic findings and the duration of clini-
CRMO bone lesions show nonspecific inflamma- cal disease (15,45). Biopsy specimens may show
tory changes with granulocytic infiltration (8,19). acute, subacute, and chronic changes mixed in
In the acute stages, there is a predominance of the same lesion (45).
polymorphonuclear leukocytes and osteoclastic
bone resorption with or without multinucleated Imaging Approach
giant cells. As the disease progresses, the pre- The imaging evaluation of CRMO should start
dominant features are lymphocytes, plasma cells, with radiographic evaluation of the symptomatic
histiocytes with occasional granulomas, and in- sites. If the radiographs are negative in the pres-
creased osteoblast activity (8). ence of significant clinical symptoms, further
The histologic findings correlate relatively well evaluation with MR imaging should be con-
with the radiologic appearance; however, some sidered to evaluate for marrow edema. When a
studies have shown poor correlation between diagnosis of CRMO is considered on the basis
of clinical findings and initial imaging evalu-
ation, further evaluation of the whole body is
RG Volume 29 Number 4 Khanna et al 1163

Figures 4, 5. (4) Bilaterally symmetric

disease in a 23-year-old woman who pre-
sented with right knee pain at the age of 9
years; the diagnosis of CRMO was made.
Tc bone scan obtained at the time of
relapse shows bilaterally symmetric uptake
in the distal femora and additional sites of
disease in the proximal right tibia, mid left
fibula, and distal left tibia. (5) CRMO in a
24-year-old woman with a 10-year history
of mandibular pain and swelling, for which
she had undergone multiple surgeries and
prolonged antifungal therapy at outside
hospitals. (a) Axial CT image shows lytic
areas in the right mandibular ramus (ar-
row) with sclerosis and bony expansion.
The associated cortical disruption was
due to prior surgery. There is associated
overlying soft-tissue swelling. (b) Postop-
erative chest radiograph obtained at our
institution shows expansion of the anterior
aspect of the left first rib (arrow), a finding
that aided in the diagnosis of CRMO.

suggested to identify multifocal lesions that may Although bilateral disease is morphologically
be clinically asymptomatic (Fig 1). Whole-body symmetric, it typically lacks clinical and temporal
evaluation has traditionally been performed symmetry. The identification of additional sites of
with 99mTc bone scintigraphy, although whole- disease can aid in the diagnosis of CRMO, espe- Teaching
body MR imaging is being increasingly used for cially when disease is present at typical locations Point
evaluation of multifocal bone lesions (4648). like the anterior chest wall or when disease is
Although MR imaging has the advantages of symmetrically distributed (Figs 4, 5). In addition,
avoiding radiation and demonstrating lesions the identification of all sites of disease aids in the
confined to the marrow, it is considerably more follow-up of disease activity.
expensive than bone scintigraphy.
Whole-body imaging can demonstrate clini- Imaging Appearances
cally occult sites of disease, confirming the mul- The findings at imaging studies can be suggestive of
tifocal nature of disease. In the series of Yu et al a diagnosis of CRMO but are not pathognomonic.
(49), imaging demonstrated 20 additional sites of Common sites of skeletal involvement include the
disease in seven children, who had clinically ap- long tubular bones and clavicle, but lesions have
parent disease at only 14 sites. In another series been described throughout the skeleton, includ-
of patients, scintigraphy demonstrated an average ing the spine, pelvis, sacroiliac joint, ribs, sternum,
of six lesions per patient, even though 12 of the scapula, mandible, and hands and feet. Involvement
14 cases had a unifocal presentation (34). In ad- of the lower extremity has been reported to be three
dition, 64% of the cases in that series were found
to have bilateral disease at scintigraphy.
1164 July-August 2009

Figure 6. CRMO in a 12-year-old girl with a 7-month history of ankle pain. (a) Anteropos-
terior radiograph of the ankle shows multiple pyramid-shaped lytic lesions with surrounding
sclerosis in the metaphyses of the tibia and fibula (straight arrow); the lesions extend across
the growth plate into the epiphysis (wavy arrow). Multiple apophyseal lesions are also present
in the tarsal bones (arrowheads). Also note the generalized osteopenia. (b) Photomicrograph
(original magnification, 100; hematoxylin-eosin stain) shows fragments of bone surrounded
by fibrous stroma, in which there are scattered inflammatory cells and macrophages. Results of
microbiologic analysis were negative and thus supportive of the diagnosis of CRMO.

Figure 7. CRMO in a 5-year-old patient with right knee pain. (a) Lateral radiograph of
the knee shows a permeative lytic pattern in the patella (arrow) with overlying soft-tissue
swelling. (b) Sagittal fat-saturated T2-weighted MR image shows erosive changes of the
ossification center of the patellar apophysis (arrow), whereas the surrounding cartilage ap-
pears intact. Other sites of nonbacterial inflammation developed in both femora and tibiae
over the next 3 years. The diagnosis of CRMO was confirmed with histopathologic analysis
and negative culture results from bone biopsy.

times more common than disease in the upper ex- tribution of CRMO, specifically its tendency to
tremity (34,49). The tibia has been reported as the involve the metaphyses and metaphyseal equiva-
most common bone involvedfor both unilateral lents, is reminiscent of hematogenous osteomyeli-
and bilateral disease (50). tis in children. However, CRMO is unique in its
The most common sites of disease are the tendency to involve the claviclean uncommon
Teaching metaphyses or metaphyseal equivalents, account- site for hematogenous osteomyelitis.
Point ing for approximately 75% of all lesions in the In the early stages, plain radiographs typi-
series of Mandell et al (34) (Figs 6, 7). The dis- cally demonstrate an osteolytic lesion located
RG Volume 29 Number 4 Khanna et al 1165

Figure 8. CRMO in a 7-year-old patient with a 4-month history of leg pain.

(a) Anteroposterior radiograph of the ankle shows a small lytic lesion adjacent
to the physis. (b) Follow-up radiograph obtained 3 months later shows the en-
larging lytic lesion with surrounding sclerosis that fades away from the lesion.
(c) Radiograph obtained 3 months later shows other lytic areas adjacent to
the physis. (d) On a radiograph obtained 4 months later, the lesions appear to
coalesce and heal without significant periosteal reaction or sclerosis.

adjacent to the growth plate in the metaphysis. may indicate a process of longer duration than
With time, progressive sclerosis is seen around suggested by the patients clinical symptoms,
the lytic lesion, so that chronic lesions may be likely due to the insidious nature of the clinical
predominantly sclerotic with associated hyper- symptoms (Fig 9) (49). Radiographic findings
ostosis. The appearance of CRMO lesions can of exacerbations include new areas of lytic de-
range between purely osteolytic, osteolytic with struction and periosteal reaction, which develop
a sclerotic rim, mixed lytic and sclerotic, and sclerosis with time, resulting in progressive hy-
purely sclerotic (Fig 8). Multiple metaphyseal perostosis and sclerosis.
lesions may be present extending along a growth
plate (Figs 6, 8). The radiographic findings
1166 July-August 2009

Figure 9. CRMO in a 6-year-old girl

with a 1-week history of right leg pain.
Anteroposterior (a) and lateral (b) ra-
diographs of the right tibia and fibula
show sclerosis of the proximal tibia with
cortical thickening, which extends into
the distal diaphysis. A small lytic lesion
is present in the mid fibula with mild as-
sociated periosteal reaction. Bone scintig-
raphy showed uptake in these lesions and
in the right femur. The histopathologic,
clinical, and culture findings were com-
patible with CRMO.

Figure 10. CRMO in an 11-year-old pa-

tient with multifocal bone pain. (a) Oblique
radiograph of the right ankle shows a lytic
lesion of the metaphysis that appears to ex-
tend across the growth plate (arrow). There
is a suggestion of overlying soft-tissue swell-
ing. (b) Sagittal fat-saturated T2-weighted
MR image shows edema involving the distal
metaphysis and extending across the physis
into the epiphysis. There is associated soft-
tissue inflammation and periosteal reaction.
RG Volume 29 Number 4 Khanna et al 1167

CRMO, 30% were noted to have joint involve-

ment with synovial thickening, joint effusion, or
destruction of joint cartilage and subchondral
bone (52). MR imaging may show small fluid
collections or areas of necrotic bone, features that
have been demonstrated in histologic studies of
CRMO as well (8). However, the presence of a
large fluid collection or abscess, fistulous tract, or
sequestrum makes the diagnosis of infectious os-
teomyelitis more likely than CRMO (51).
MR imaging is useful for follow-up of lesions
during exacerbation of disease, especially when
radiographs show marked sclerosis or hyperosto-
sis. Areas of new activity demonstrate high signal
intensity on T2-weighted images and contrast en-
hancement due to marrow edema, with the sur-
rounding sclerotic bone appearing hypointense
on both T1- and T2-weighted images.
Note that CRMO shares many features with
chronic sclerosing osteomyelitis of Garr. Both
entities are seen in children and adolescents and
are characterized by an insidious onset, a relaps-
ing-remitting course, negative culture results, and
lack of suppuration. Both entities tend to involve
the long tubular bonesmainly the femur or
tibia. It is likely that CRMO and chronic scleros-
ing osteomyelitis of Garr are different names
given to the same disease (45).

Tubular Bones
Figure 11. Soft-tissue inflammation in an 11-year-
The most common location of disease in the
old girl with known CRMO and a 2-year history of
chest pain. (a) Posteroanterior radiograph of the chest tubular bones is the metaphysis adjacent to
shows an expanded right third rib (arrow). (b) Axial the growth plate (over 50%), followed by the
contrast materialenhanced T1-weighted MR image diaphysis, diaphyseal-metaphyseal region, and
of the chest shows marked soft-tissue inflammatory metaphyseal-epiphyseal region (34). The typi-
changes around the rib (arrow), a finding that can cal finding in the long tubular bones is a round
mimic a malignancy like Ewing sarcoma. Biopsy re- or column-shaped osteolytic metaphyseal lesion
vealed sterile inflammation. abutting the growth plate (Fig 6). The lytic le-
sion becomes surrounded by a thin, sclerotic
zone within 12 weeks (15). As the inflamma-
MR imaging is useful both for determining tory process extends into the cortex, periosteal
the extent of disease and for surveillance. Dur- reaction develops, which can be quite extensive
ing the active phase of the disease, MR imaging in long tubular bones.
shows typical findings of marrow edema, which The amount of periosteal reaction depends on
appears hypointense on T1-weighted images and both the duration of disease and the anatomic site
hyperintense on T2-weighted images. MR imag- involved. Although small-diameter bones like the
ing can demonstrate associated periostitis, soft- fibula and metacarpals-metatarsals can have exten-
tissue inflammation, and transphyseal disease sive periosteal reaction and soft-tissue inflamma-
findings that are typically underestimated on tion, lesions in large-diameter bones like the femur
radiographs (Figs 10, 11) (39,51). The detection can have a predominantly lytic-sclerotic process
of transphyseal involvement may have prognostic with minimal surrounding reaction (Fig 12). It has
significance by allowing identification of patients been suggested that small-diameter bones dem-
at higher risk for growth deformities due to for- onstrate more periosteal reaction owing to earlier
mation of physeal bars (22). extension of the inflammatory process from the
Clinically occult joint effusions adjacent to medullary space into the cortex (22). The marked
the osseous lesions can be demonstrated with
MR imaging (28). In a series of 66 patients with
1168 July-August 2009

Figure 12. CRMO of tubular bones in a 7-year-old girl with a 5-year history of multifocal bone pain. (a) Radio-
graph of the ankles shows multiple lytic lesions with surrounding sclerosis adjacent to the growth plate in both tibias
and fibulas. The physes and epiphyses appear to be spared. (b) Follow-up radiograph obtained 7 years later shows
bilaterally symmetric hyperostosis of the fibula without significant periosteal reaction in the tibia.

periosteal reaction and sclerosis seen with CRMO

lesions of tubular bones has also been referred to
as tumorous osteomyelitis (Fig 2) (20).
Chronic inflammation at the metaphysis can
Teaching result in abnormal tubulation of the long bones
Point with metaphyseal expansion and sclerosis, a use-
ful imaging finding in long-standing CRMO (Fig
12). Although the inflammation can extend into
the cortex, the presence of cortical disruption
should raise concern for an aggressive lesion,
such as a malignancy, and further evaluation with Figure 13. CRMO of the clavicle in a 7-year-old boy
a biopsy should be performed (53). with a 1-year history of CRMO. Plain radiograph of the
left clavicle shows sclerosis and expansion of its medial
Clavicle aspect (arrow), while the lateral aspect is normal.
CRMO of the clavicle most commonly manifests
with local swelling, pain, or impairment of shoul-
der movement and may cause thoracic outlet Clavicular CRMO is unique compared with
syndrome (54). Like CRMO in other parts of the the other common sites of disease in CRMO, in
body, clavicular involvement appears to be more that hematogenous osteomyelitis of the clavicle is
common in female patients than in male patients. extremely uncommon. CRMO of the clavicle has
CRMO is the most common nonneoplastic pro- been referred to by several different names, includ-
cess involving the clavicle in patients less than ing recurrent hyperostosis of the clavicle, sterno-
20 years of age (55). It is also the most common costoclavicular hyperostosis, idiopathic cortical hy-
Teaching disease process to involve the medial third of perostosis, and condensing osteitis of the clavicle
Point the clavicle in all age groups (55). Up to 30% (56,57). There seems to be a higher prevalence of
of all CRMO lesions are located in the clavicle clavicular disease in CRMO patients with palmo-
(40). Given the preceding facts, the diagnosis of plantar pustulosis and acne fulminans (14).
CRMO should be considered in the differential Clavicular disease typically manifests as a lytic
diagnosis of a sclerotic expanded lesion affecting medullary process in the medial part of the clav-
the medial third of the clavicle in children and icle with surrounding periosteal reaction, which
adolescents (Fig 13). Considering this diagnosis may have an onion skin appearance. During
can help avoid unnecessary biopsies and anxiety remissions, the lesions heal with progressive scle-
for patients, secondary to a misdiagnosis of a ma- rosis. With each exacerbation, the disease tends
lignancy such as Ewing sarcoma (55,56). to extend laterally, although the most lateral part
of the clavicle remains unaffected (58). CRMO
RG Volume 29 Number 4 Khanna et al 1169

Figure 14. CRMO of the

spine in a 4-year-old boy with
back pain. (a) Lateral radio-
graph of the lumbar spine
shows sclerosis of the L3 ver-
tebral body (arrow). (b) Axial
CT image shows sclerosis and
permeative lytic changes in
the vertebral body and exten-
sion into the right pedicle
(arrow). (c) Axial postcontrast
T1-weighted MR image shows
extension of the inflammatory
process into the adjacent para-
vertebral soft tissues. Biopsy
revealed chronic inflammatory
changes with no organism

in children is characterized by progressive hy- the sclerotic-hyperostotic clavicular lesions tend

perostosis and sclerosis of the medial end of the to persist for several years and can cause thoracic
clavicle without involvement of the sternoclavicu- outlet syndrome (41).
lar joint. This is in contradistinction to clavicular
involvement in adults with CRMO; such in- Spine
volvement occurs as a subphenotype of SAPHO Spinal involvement, although less common than
syndrome, in which clavicular disease is often ac- disease in the long tubular bones, has been re-
companied by arthritic changes of the joint space ported in CRMO. In a review of 35 cases of
(58). Also, the ligamentous ossification and bony CRMO with 157 lesions, only 3% of lesions
bridging across the sternoclavicular joint reported were present in the vertebral bodies (12). How-
in adults have not been described in children. ever, CRMO of the vertebral body is the most
Radiographic evaluation of the clavicle can be common site to be complicated by a pathologic
limited due to overlapping structures. CT can fracture (28). Spinal disease may be detected
more clearly demonstrate the extent of disease incidentally during the radiologic work-up of sus-
with lytic areas and surrounding sclerosis and pected CRMO, or it may be the site of primary
hyperostosis. MR imaging reveals bone mar- presentation. Presenting symptoms can include
row edema with surrounding periosteal reac- back pain, scoliosis or kyphosis, and rarely cord
tion. Inflammatory changes can also be seen compression (59).
extending into the surrounding soft tissues and Radiologic findings include partial or complete
muscles; these changes may give the appearance loss in height of the vertebral body. A lytic lesion
of an aggressive process such as Ewing sarcoma, with surrounding sclerosis or a purely sclerotic ap-
lymphoma, or histiocytosis (54). With increas- pearance may be seen in the vertebral body with
ing sclerosis and hyperostosis, both T1- and T2- or without extension into the pedicle (Fig 14). The
weighted images show markedly hypointense ar- thoracic spine is the most common site of disease
eas. New areas of activity can be identified in the (accounting for 46 of 65 spinal lesions in one re-
hyperostotic clavicle as hyperintense lesions on view), followed by the lumbar spine (13 of 65),
T2-weighted images, in cases where radiographic while disease in the cervical spine and sacrum is
evaluation may be limited due to overlapping less common (60).
structures and hyperostosis. Whereas the meta-
physeal lesions of long bones can heal completely,
1170 July-August 2009

Figure 15. CRMO of the spine in a 6-year-old boy with multifocal bone pain for 1 year.
(a) Anteroposterior radiograph shows marked loss in height of the T4 vertebral body (arrow)
and partial collapse of the T7 and T8 vertebral bodies with endplate irregularity (arrowhead).
(b) Sagittal T2-weighted MR image shows a vertebra plana at T4. Spondylodiskitis is seen at
T7-8 with endplate irregularity, but disk height and signal intensity are preserved.

Figure 16. CRMO of the spine in a 6-year-old girl with a history of back pain. Radiogra-
phy showed some loss in height of the T9 vertebral body. (a) Sagittal T1-weighted MR image
shows loss of normal marrow signal intensity in the T2, T9, T10, and T12 vertebral bodies
with loss in height of T9. (b) T2-weighted MR image shows edema in the T9 vertebral body
with a low-signal-intensity line paralleling the inferior endplate (arrow). Note that the inter-
vertebral disk space appears unremarkable even in the presence of contiguous vertebral body
RG Volume 29 Number 4 Khanna et al 1171

MR imaging demonstrates altered signal

intensity of the vertebral marrow and partial or
complete loss in height of the vertebral body. The
adjacent disk may show some loss in height or al-
tered signal intensity; however, to our knowledge,
none of the reported cases have shown extension
of disease across the intervertebral disk spacea
feature that can help differentiate CRMO from
infectious osteomyelitis (Fig 15) (60,61). A sub-
chondral fracture-like line has also been reported
in CRMO patients with vertebral collapse, but
there are no data on the specificity of this finding
for a diagnosis of CRMO (Fig 16) (60). MR imag-
ing often demonstrates additional sites of disease
in the spine that are occult at clinical examination,
Figure 17. CRMO of the pelvis in a 9-year-old girl radiography, or scintigraphy (Fig 16) (61,62).
with multifocal bone pain since the age of 2 years. An- Involvement of multiple noncontiguous ver-
teroposterior radiograph of the pelvis shows multiple tebral bodies with sparing of the intervening
lytic lesions with sclerotic margins at both ischiopubic
disks helps differentiate CRMO from infec-
synchondroses (arrows); the lesions extend into the
ischial tuberosities.
tious osteomyelitis. Although histiocytosis X
remains the most common cause of vertebra
plana in children, CRMO is another disease that
can cause vertebra plana (49). Since the initial
description in 1989, several cases of vertebra
plana secondary to CRMO have been reported
(49,51,6365). Unlike in vertebra plana caused
by eosinophilic granuloma, restitution of verte-
bral body height has not been observed in verte-
bra plana caused by CRMO (49).

CRMO of the pelvis is less common. The sites of
predilection in the pelvis include the metaphyseal
equivalentssuch as the ischiopubic synchondro-
sis and the sacroiliac jointssites that are prone
to hematogenous osteomyelitis as well (Fig 17).
These lesions may be subtle on radiographs; how-
ever, cross-sectional imaging with CT will clearly
demonstrate the osteolysis with surrounding pe-
riosteal reaction and sclerosis. MR imaging shows
edema in active lesions with surrounding periosti-
tis and associated soft-tissue inflammation.
Because the synchondroses have avidity for
Tc, bone scans should be evaluated carefully
at single-photon-emission CT for any asymmetry
of activity, to identify pathologic sites. CRMO of
the pelvic synchondrosis tends to heal without
significant sequalae (66). Pelvic disease can also
manifest as sclerosis of bones such as the iliac
wings. During evaluation of the pelvis, close at-
tention should be paid to the sacroiliac joints,
as patients with CRMO are at increased risk of
Figure 18. CRMO of the pelvis in a 7-year-old boy
developing spondyloarthropathy with unilateral
with biopsy-proved CRMO who presented with back
pain. (a) Pelvic radiograph shows widening of the left sacroiliitis (Fig 18) (42).
sacroiliac joint (arrow). (b) Axial CT image shows
marked erosive changes along the iliac aspect of the
joint (arrow) with joint space widening, findings con-
sistent with unilateral sacroiliitis.
1172 July-August 2009

Figure 19. CRMO of the mandible in an 8-year-old girl with a 10-week history of man-
dibular pain and swelling. (a) Axial maxillofacial CT image shows marked sclerosis and
expansion of the mandible with multiple lytic foci. (b) Axial maxillofacial CT image shows
that the sclerosis and expansion also involve the right maxilla and zygoma (arrow).

Mandible among oral surgeons, is essential to avoid un-

CRMO can involve the mandible in about 5% of necessary antibiotic therapy and multiple invasive
cases (40). Mandibular CRMO has also been re- procedures (Fig 5).
ferred to as diffuse sclerosing osteomyelitis of the
mandible (6769). It typically manifests as chronic Hands and Feet
mandibular pain, although associated jaw swell- CRMO is more common in the small bones of
ing may also occur. Mandibular disease can be the feet than in the hands. It can involve the tar-
isolated or accompanied by disease at other sites sal bones such as the calcaneus and talus, which
in the body. In a review of 12 adult cases of diffuse are metaphyseal equivalents, or the short tubular
sclerosing osteomyelitis of the mandible, 50% were bones including the metatarsals and phalanges
found to have disease at other sites such as the (Fig 20). The short tubular bones typically dem-
anterior chest and spine (68). Mandibular disease onstrate lytic lesions with surrounding sclerosis,
has also been shown to be associated with lesions periosteal reaction, and associated soft-tissue
in other skull or facial bones such as the maxilla inflammation (Fig 21). CRMO of the metatarsals
and zygoma (Figs 1, 19) (69,70). and phalanges has been reported to cause prema-
Radiographic findings are similar to those in ture physeal closure (22).
other sites of disease, with initial stages demon-
strating a lytic process with associated variable Differential Diagnosis
amounts of sclerosis. Cross-sectional imaging The differential diagnosis of CRMO includes
often reveals associated soft-tissue inflamma- subacute and chronic infectious osteomyelitis,
tion as well, without evidence of discrete abscess histiocytosis, hypophosphatasia, and malignancies
formation. As the mandibular disease progresses, like leukemia, lymphoma, and Ewing sarcoma
increasing sclerosis with hyperostosis and pro- (71). Although the typical imaging findings of
gressive enlargement of the mandible develop. CRMO can aid in suggesting the correct diagno-
Biopsy results reveal a culture-negative chronic sis, they are not pathognomonic.
osteomyelitis. Awareness of this entity, especially Clinical and radiographic features that help in
differentiating CRMO from infectious osteomy-
elitis and tumors include the following: (a) a pro-
longed clinical course, with most patients being
RG Volume 29 Number 4 Khanna et al 1173

Figures 20, 21. (20) CRMO of the foot in an

8-year-old patient with a 1-year history of biopsy-
proved CRMO who presented with new-onset heel
pain. (a) Lateral radiograph of the ankle shows sclero-
sis of the calcaneus (arrow) adjacent to the physis with
overlying soft-tissue swelling. (b) Sagittal T1-weighted
MR image shows edema of the posterior calcaneal
apophysis (arrow) with mild surrounding soft-tissue
inflammation. The diagnosis of nonbacterial osteomy-
elitis was confirmed with biopsy. (21) CRMO of the
foot in a 12-year-old girl with a 1-year history of ankle
and foot pain. Anteroposterior radiograph of the foot
shows generalized osteopenia. A subphyseal lytic lesion
is seen in the first proximal phalanx (arrow). Multiple
other oval, peripherally sclerotic lesions (arrowheads)
are present in the metatarsal and tarsal bones. The
clinical features, histopathologic findings, and culture
results were compatible with a diagnosis of CRMO.

The disease course of CRMO is unpredictable.
Although most cases undergo spontaneous resolu-
tion in several months to several years, patients
have been found to be symptomatic for as long as
healthy between recurrent episodes; (b) an un- 25 years after the initial diagnosis (72). In a study
usual location of lesions in comparison with those of 13 patients, Jurik et al (66) found all cases to be
of infectious osteomyelitis, such as involvement symptomatic after a follow-up period of 16 years,
of the clavicle, bilateral symmetry, and frequent although in most cases symptoms related to the
multifocality; (c) radiographs showing multiple initial lesions had resolved. In contrast, long-term
foci of osteolysis with associated sclerosis or hy- follow-up of a German cohort revealed all cases
perostosis; (d) lack of abscess formation, fistulas, to be in remission (19). In a follow-up study of 23
or sequestra; (e) lack of response to antibiotics; patients, Huber et al (50) showed that 25% of sub-
and (f) comorbid inflammatory disorders such as jects had persistent signs of disease activity when
psoriasis, palmoplantar pustulosis, or inflamma- evaluated at a median time of 12.4 years after di-
tory bowel disease (19,51). Because the imaging agnosis. In the follow-up study of Duffy et al (72),
findings of CRMO can be nonspecific, especially the shortest duration of symptoms was 2.5 years
early in the course of the disease, evaluation of and the longest duration was 20 years.
the osseous lesions with biopsy and culture is re-
quired to establish a diagnosis of CRMO.
1174 July-August 2009

Although most CRMO lesions heal to become CRMO. Furthermore, the skin lesions may mani-
occult at radiography, others can demonstrate fest several years after the first bone lesion in chil-
persistent sclerosis. Persistent sclerosis appears dren with CRMO (43).
to be the pattern in older patients, in whom the Whereas chest wall and pelvic disease pre-
normal modeling and growth process of bone is dominates in SAPHO syndrome, the long bones
already complete. Lesions occurring in skeletally are the most common sites of disease in CRMO.
immature children may undergo restitution to This is likely related to the presence of open
normal bone. This might not be true in bones physes in children predisposing to a higher prev-
that have developed marked hyperostosis, with alence of metaphyseal lesions, as is seen in he-
sclerosis extending into the medullary cavity. One matogenous osteomyelitis. CRMO and SAPHO
example of this is the clavicle, where the hyper- syndrome differ in the type of disease seen at the
ostosis can produce a palpable bump and be a anterior chest wall. Although involvement of the
source of thoracic outlet obstruction (41). An- sternoclavicular and first sternocostal joint and
other residual deformity is thoracic kyphosis sec- ossification of the costoclavicular ligaments are
ondary to vertebral body compression (37,66). frequent in SAPHO syndrome, these findings
CRMO of long bones can result in orthope- are not reported in CRMO.
dic complications like bony overgrowth, angular Adults with SAPHO syndrome can have arthri-
deformities, and limb-length discrepancy at ma- tis of peripheral joints and ossification of ligaments
turity (72). Owing to its tendency to occur near and entheses, features not typically seen with
the physes, CRMO can cause premature physeal CRMO (66). Children with CRMO have been re-
closure, resulting in growth arrest. Manson et al ported to have arthritis at sites distant from the os-
(22) described six sites of premature physeal fu- teomyelitis lesions. Whether CRMO and SAPHO
sion among 29 sites of disease in seven patients syndrome are distinct diseases or the same disease
with CRMO. Premature physeal fusion has been process with differences in phenotype based on
reported most often in the metatarsals, followed age of onset remains to be determined.
by the tibia and femur (22,41). Limb-length
discrepancy has been reported to be the most Summary
common physical deformity in patients with a CRMO is an established clinicopathologic entity,
history of CRMO, with the affected limb being although its cause remains elusive. Along with the
shorter in most cases (72). The hyperemia caused variability in its initial presentation, there is great
by chronic inflammation may result in diffuse de- variability in the numbers of sites affected, recur-
mineralization, predisposing to fractures (73). rence rates, and prognosis. The typical clinical
An increased risk of chronic spondyloar- picture of CRMO is a child or young adult with a
thropathy, unilateral sacroiliitis, and enthesitis has history of chronic multifocal bone pain, in whom
also been suggested in children with a history of biopsy of osseous lesions shows osteomyelitis with
CRMO in the absence of a human leukocyte an- failure to culture any organisms. The typical radio-
tigen (HLA)B27 association (21,42,43). In the graphic appearance is a lytic lesion at a metaphysis
study of Vittecoq et al (42), 12 of 15 patients with or metaphyseal equivalent that develops progres-
CRMO developed spondyloarthropathy that met sive sclerosis and hyperostosis over time.
the criteria of the European Spondyloarthropathy With the exception of CRMO in the context of
Study Group, with spine involvement developing Majeed syndrome, there is no diagnostic test for
after a median follow-up of 5.63 years. CRMO and it remains a diagnosis of exclusion.
The presence of disease in typical sites such as the
CRMO versus SAPHO Syndrome medial clavicle, the presence of bilateral disease in
SAPHO syndrome is the adult equivalent of a symmetric distribution, and the presence of skin
CRMO. Whereas CRMO typically manifests in findings such as palmoplantar pustulosis support
the first decade of life, the mean age of onset for the diagnosis. Diagnosis of CRMO requires a team
SAPHO syndrome is 28 years (74). However, approach between the pediatric rheumatologist,
adults with CRMO and children with SAPHO orthopedic surgeon, radiologist, and pathologist.
syndrome have been reported (40,75). The preva- Radiologists need to be familiar with the imaging
lence of skin lesions like palmoplantar pustulosis findings because they may be the first to suggest
is much higher in SAPHO syndrome than in this diagnosis. This can help minimize the number
of unnecessary interventions in the form of re-
peated biopsies, surgeries, and antibiotic therapy.
RG Volume 29 Number 4 Khanna et al 1175

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This article meets the criteria for 1.0 AMA PRA Category 1 Credit TM. To obtain credit, see
RG Volume 29 Number 4 July-August 2009 Khanna et al

Imaging of Chronic Recurrent Multifocal Osteomyelitis

Geetika Khanna, MD, MS, et al
RadioGraphics 2009; 29:11591177 Published online 10.1148/rg.294085244 Content Codes:

Page 1163
The identification of additional sites of disease can aid in the diagnosis of CRMO, especially when
disease is present at typical locations like the anterior chest wall or when disease is symmetrically
distributed (Figs 4, 5).

Page 1163
Common sites of skeletal involvement include the long tubular bones and clavicle, but lesions have
been described throughout the skeleton, including the spine, pelvis, sacroiliac joint, ribs, sternum,
scapula, mandible, and hands and feet.

Page 1164
The most common sites of disease are the metaphyses or metaphyseal equivalents, accounting for
approximately 75% of all lesions in the series of Mandell et al (34) (Figs 6, 7).

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Chronic inflammation at the metaphysis can result in abnormal tubulation of the long bones with
metaphyseal expansion and sclerosis, a useful imaging finding in long-standing CRMO (Fig 12).

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It is also the most common disease process to involve the medial third of the clavicle in all age
groups (55).