Description
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, non-infectious inflammatory disorder affecting the skeletal system. Characterised by multifocal bone lesions that recur over time, it typically presents in childhood or adolescence.
CRMO is considered a subtype of Chronic Non-bacterial Osteomyelitis (CNO) which is an umbrella term that includes both unifocal and multifocal varieties of the disease. When the disease presents as multiple bone lesions that have a recurrent and chronic course, it is specifically referred to as CRMO.
Pathogenesis
The exact pathogenesis of CRMO is unknown, although it is thought to result from a combination of genetic predisposition and an abnormal immune response. This leads to chronic inflammation and bone remodelling. While it is non-infectious, the inflammatory process mimics that of an infection.
Epidemiology, Risk Factors & Associations
- CRMO most commonly presents in children and adolescents (9-14 years), although it can occur at any age.
- The incidence is estimated to be 1:1,000,000, with a slight predominance in females.
- Associations include other inflammatory conditions such as psoriasis, inflammatory bowel disease, and ankylosing spondylitis.
Clinical Features
- Recurrent episodes of bone pain, swelling, and warmth.
- Lesions can occur in any bone but are most commonly found in the metaphyses of long bones (lower extremities, more than upper extremity), clavicles (classically medial aspect), and vertebrae.
- Fever and malaise may be present during flare-ups.
- Some patients may have associated skin lesions, including pustulosis palmaris et plantaris and severe acne.
Complications
Potential complications include permanent bone deformity, pathological fractures, and secondary amyloidosis.
Subtypes
There are no defined subtypes of CRMO.
Pathological Features
Morphology
Areas of bone destruction and new bone formation.
Histopathology
Typically reveals chronic inflammation with lymphocytes and plasma cells. Neutrophils may also be seen, mimicking infectious osteomyelitis.
Biochemistry/Genetics
There is no specific genetic mutation associated with CRMO, but there may be familial clustering in some cases.
Radiological Features
General Imaging Features
- Typically presents as lytic lesions with surrounding sclerosis, commonly affecting the metaphysis of long bones, tibia/femur, spine, pelvis, and medial clavicles.
- It is the most common disease to involve the medial clavicle.
- Lesions are often symmetric and multifocal.
- Chronic lesions can develop a ‘bull’s eye’ appearance with central sclerosis surrounded by a radiolucent ring.
X-ray
- Initial presentation may be radiolucent (osteolytic) areas with irregular borders. As the disease progresses, the lesions become more sclerotic.
CT
- Can delineate the ‘bull’s eye’ appearance in chronic lesions. It can also help detect subtle lesions in the early stages of the disease.
MRI
- Most sensitive imaging modality for CRMO – demonstrates bone marrow oedema, which represents active inflammation.
- Soft tissue and periosteal oedema
- Reactive adjacent joint effusion/synovitis
- After contrast administration, an enhancing rim can be seen around the lesions.
- T1WI: Low signal observed within the metaphysis adjacent to the growth plate.
- T2WI FS/STIR:
- Focal, well-circumscribed, peri-epiphyseal metaphyseal lesion of increased signal.
- Possible breach of physis, potentially leading to subsequent growth arrest.
- Less pronounced, poorly defined increased signal in the bone marrow of the adjacent meta-diaphysis and epiphysis.
- Epiphyseal signal may be disproportionate to physeal involvement.
- Possible presence of periosteal/soft tissue oedema or inflammation.
- Potential for small, reactive, adjacent joint effusion.
- T1WI C+ FS:
- Diffuse enhancement of bone and soft tissue abnormalities.
- Absence of drainable soft tissue or subperiosteal collection.
- Possible small foci of peripheral enhancement in bone, potentially due to sterile intraosseous abscess or necrosis.
- Potential for mild synovial thickening and enhancement in adjacent joints.
Nuclear Medicine
- Technetium-99m bone scintigraphy can be used to identify multifocal involvement, showing increased uptake in the areas of active disease.
Grading and Staging
There is no specific grading or staging system for CRMO.
Differential Diagnosis
- Infectious Osteomyelitis: Clinical presentation can be very similar. However, patients with infectious osteomyelitis are often more acutely unwell (rather than a prolonged clinical course), and investigations usually identify an infectious organism.
- Ewing Sarcoma: This can present with similar symptoms and bone changes. A key differentiating feature is the presence of a soft tissue mass in Ewing sarcoma, which is not typically seen in CRMO. Also, Ewing sarcoma is more likely to have a ‘onion-skin’ periosteal reaction on radiological imaging.
- Langerhans Cell Histiocytosis (LCH): LCH can also cause lytic bone lesions. However, these lesions are typically more destructive, and other systemic symptoms such as diabetes insipidus or skin rash may be present in LCH.
Management
Management is primarily medical and aimed at controlling inflammation and pain. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often first-line treatment, with corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), and biologic agents used for refractory cases. Bisphosphonates may be used to promote bone healing. Consultation with rheumatology is recommended. If diagnostic uncertainty exists, a bone biopsy may be performed to rule out other causes of bone lesions.