Acute non-bacterial multifocal osteomyelitis

A 9-year-old boy is admitted to our facility for a recent onset of fever and joint pain prevalent in pelvis and lower limbs. The clinical evaluation demonstrates mild joint swelling at the left tibiotarsal joint. Laboratory tests show an inflammatory condition: CPR 49,20 mg/l , ESR 36 mm/h, WBC 11,520 x 109/L, INR 1,43.

Ankle radiograph: lucent lesion with distinct sclerotic margins to the distal metaphysis of the tibia with a broad relationship with the growth plate. AP pelvis radiograph: the right acetabular roof has irregular contours.

Ankle MRI: At the distal metaphysis of the left tibia, a lesion with axial dimensions of 18 x 10 mm hypointense in T1, isointense in T2 and hyperintense in fat suppression sequences is observed. The lesion is surrounded by bone marrow and soft tissue oedema in the absence of abscess or sinus-tract. The edges of the lesion are well-defined and with slight signs of reactive sclerosis. Small tibiotalar effusion.

Pelvic MRI: an area of bone marrow oedema is observed at the right acetabular roof, in relation to the growth cartilage. Further areas of bone marrow oedema were found in the quadrilateral lamina and ischiopubic lamina on the left.

The first description of non-bacterial symmetric chronic osteomyelitis occurred in 1972 [1] this the pathological entity was defined as CRMO in 1978 [2]. Currently, it is preferred to use as a term nonbacterial osteomyelitis (NBO), to indicate all those bone inflammatory conditions without a pathogen. In relation to the time of onset and the clinical course, acute (ANBO), chronic (CBO) and chronic recurrent multifocal (CRMO) forms are distinguished [3], it can also be associated to an inflammatory condition of the skin (psoriasis, severe acne), the intestine (inflammatory bowel disease), and the joints (arthritis, sacroiliitis) also in syndromic forms (es. SAPHO), and autoimmune diseases. It appears that the condition results from an imbalance between pro- and anti-inflammatory cytokine expressions in monocytes [4-5].

The disease is rare but probably underestimated [6], is more frequent in children but can affect any age group [7].  The metaphysis of the long bones are involved in about 75% of cases, but all other bones can also be affected [8]. Spine and clavicle are well-known localizations [9-10].

The consistent feature of the non-bacterial osteomyelitis is the insidious onset of pain with swelling and tenderness localised over the affected bones.

The bone changes in the NBO are several, the most frequent is certainly osteitis (70%) for which the MRI evaluation is essential. Other typical signs such as the presence of lytic lesions (20%), hyperostosis (20%) and bone deformity (20%) are rarer and often later findings, which can also be demonstrated on radiographs [11] as in this case. Unlike bacterial forms, abscesses or fistulas are not shown [12].

Especially in acute forms of non-bacterial osteomyelitis radiographic exams can be negative, so MRI is the fundamental exam to confirm clinical-radiological suspicion and to plan the biopsy approach. When the diagnosis is suspected the search for further inflammatory foci with total body MRI is advisable [13].

A bone biopsy on the tibial lesion, negative for pathogens oriented towards the correct diagnosis. The presence of genetic alterations linked to NBO has been demonstrated in the mouse genome [14], but it has only been detected in humans in a small percentage. This opens up new diagnostic and therapeutic possibilities for this still rather unknown disease [15].

Take-Home Message

Non-Bacterial Osteomyelitis is an underestimated disease, especially in the acute form. For the early detection of NBO the use of magnetic resonance imaging, in the adequate clinical context, is mandatory.  Imaging is often inconclusive for diagnosis, but it can help to rule out other conditions and orientate diagnosis to facilitate a correct and early therapeutic approach.

Written informed patient consent for publication has been obtained.