3 steps to WHO?

1. CRMO usually affects children on average 10 yo with predilection to girls (twice as high as boys). SAPHO syndrome  usually affects adults (defined by us as completed skeletal growth). More than ⅔ of CNO patients are female [4].
2. CRMO or SAPHO syndrome may coexist with autoinflammatory diseases, for example inflammatory bowel diseases, giant cell vasculitis or granulomatosis with polyangiitis.
3. Sporadically, CRMO may be part of syndromes, such as Majeed syndrome, Sweet syndrome or PAPA syndrome.

3 steps to WHERE?

Inflammation can affect all sites of the skeleton, however the most common sights on involvement are (tbl 1):

Fig 24: Tbl 1. Typical locations of CRMO/SAPHO lesions in children and adults. The...

1. in children: clavicles (30% lesions in CRMO [1]),  metaphyses and diaphyses of long bones (especially tibiae) with quite common involvement of the nearest joints; sometimes - mandible;
2. in adults: anterior chest wall (with the most characteristic involvement of sternoclavicular joints, followed by the sternum and costo-sternal junctions of the upper ribs) and axial skeleton (mostly thoracic spine - second commonest site of involvement in all ages, and sacroiliac joints);
3. Multifocal distribution is very common - look for it!

3 steps to WHAT?

       1. Look for two of the most important radiological findings:

Fig 3: Imaging studies (X-ray, CT, and MRI) of 32 yo female with monofocal SAPHO...

Hiperostosis - thick cortical bone with narrow medullary canal due to prominent endosteal and periosteal reaction 

Osteitis - in the compact bone seen as osteolytic foci and in cancellous bone characterised by resorption areas and sclerosis of trabeculae.

Fig 2: 1-2: MRI of the patient from Picture 1 shows an active phase of the disease...

At the beginning of the disease lesions are mostly osteodestructive with more osteoproliferative course over time.

Fig 14: 10-14: CT showing the evolution of the disease during 6-month observation....

Moreover you may find:

• arthritis with its typical symptoms: joint effusion, periarticular osteopenia, bone erosions, and ankylosis (sacroiliitis is possible as well)
• inflammatory enthesopathy
• inflammation of the soft tissues surrounding the affected bones and joints 

BUT abscesses or fistulae are never seen. 

Assessing the severity of the disease in the sterno-costo-clavicular junction you may use a three-stage scale (modified from [3])

Stage 1: lesions localised to the area of the costoclavicular ligament with a presence of soft-tissue swelling, erosion and enthesopathy;

Stage 2: progression to the sternoclavicular joint arthropathy with osteitis and  hyperostosis of the adjacent bones and potential ankylosis of the joint;

Stage 3: osteitis and hyperostosis involving the manubriosternal junction and upper ribs with sclerotic hypertrophy of the costal cartilage.

Fig 16: 16-17: The 3rd stage of the severity of the disease in the...

       2. When you assess spinal lesions watch out for 5 features: 

• non-specific spondylodiscitis (Andersson lesion) presenting as focal cortical erosions and subchondral sclerosis in the endplates at different consecutive or non-consecutive spinal levels, with or without disc space reduction, bone block formation; 
• vertebral body corner lesions (Romanus lesion) that are usually seen as an inflammation of the anterior vertebral endplates at Sharpey’s fibers’ attachement, but may as well go along the whole endplates and frontal wall of the vertebrae;
• osteodestructive lesions with a variable degree of vertebral body collapse with no history of trauma, in children with possible vertebra plana deformity;
• osteosclerosis adjacent to endplates or cortical erosive changes with potential of progression to diffuse sclerosis of the vertebral body similar to “an ivory vertebra” and vertebral enlargement due to hyperostosis;
• paravertebral ossification - marginal or nonmarginal, asymmetric syndesmophytes or bony bridging.
  

  Fig 23: Enlarged images of the thoracic spine X-ray and MRI of 35 yo male diagnosed...

As you could notice, these signs aren’t specific and may mimic spondyloarthropathies or infectious spondylodiscitis. 

Keep in mind that anteriorly to the vetrebrae soft-tissue swelling has to be less than 1 cm in thickness, which is an important difference between septic osteomielitis. Also, paravertebral abscesses are never seen.  

       3. One of the important features are skin lesions, coexisting with chronic non-bacterial osteomyelitis in 20% cases. Pustular psoriasis and severe acne are associated with SAPHO syndrome in more than 50% and almost 20% of cases, respectively. Skin lesions may occur before (the most common pattern), simultaneously, or after the onset of skeletal manifestations. 

CRUCIAL STEPS FOR EFFECTIVE DIAGNOSIS

       A. Recognize the most typical symptoms - hyperostosis and osteitis 

       B. Always ask for skin lesions: some types of psoriasis (palmoplantar pustulosis, generalised pustular psoriasis) and severe acne (acne fulminans, acne conglobata, hidradenitis suppurativa)

       C. Look for typical sites of involvement and suggest the further proceeding  (tbl 3)

Fig 26: Tbl 3. A diagram how to report when our single examination shows typical...

The easiest situation:

An adult with typical findings in the anterior chest wall on X-ray or CT → no further radiologic examinations are needed, suggest SAPHO syndrome

A child with monofocal disease confined to the clavicle → suggest CRMOMore complicated situation:

A child with monofocal disease other than clavicle → look for multiple sites of involvement, eg. proceed with WB-MRI or scintigraphy→ if multifocal suggest CRMO → if limited to one bone except for the clavicle suggest bone biopsy 

The most complicated situation:

Spine or sacroiliac joints affected → unspecific for CNO, look for another sites of involvement, differential diagnostic needed

       D. Look for multiple sites of involvement (tbl 2)

Fig 25: Tbl 2. Diagnostic path in case of suspected CRMO/SAPHO syndrome.

All of the following exams highlight subclinical, quiescent and radiographically occult sites. Unfortunately X ray changes are revealed after about 3 weeks after the onset of clinical symptoms. The unifocal lesions are present in around only 22.2% of patients [4].

Whole-body MRI (WB-MRI) (with sagittal STIR imaging of the spine) -it reveals more lesions per person than X-ray and scintigraphy according to [4]; even ⅔ of lesions shown on WB MRI are asymptomatic. Active lesions are characterized by bone marrow oedema and associated periostitis.

99mTc-MDP whole-body bone scintigraphy (WBBS) or 18FDG-PET/CT - differentiation between active and inactive lesions, and also inflammatory and neoplastic lesions. Anterior chest wall involvement produces the pathognomonic “bull head sign”.

Fig 18: “Bull’s head sign” in scintigraphy - pathognomonic sign for SAPHO...

       E. If not sure, differentiate with: (tbl 6A and B) 

YOUNGER PATIENTS:

Septic osteomyelitis 

Metabolic disease

Neoplastic disease 

Bone tumour

Iatrogenic (bisphosphonates)

Rare disease with osteosclerotic manifestations

ELDER PATIENTS:

Sclerotic metastasis

Spondyloarthropathies

Paget disease

Erdheim-Chester disease

Myelofibrosis

Sickle cell disease

Fig 29: Tbl 6 A and B. Differential diagnosis of CRMO and SAPHO syndrome.

Fig 30: Tbl 6 A and B. Differential diagnosis of CRMO and SAPHO syndrome.