A child with Chronic Nonbacterial Osteomyelitis and celiac disease: accidental association or two different aspects of the same condition?

Abstract

Background: Chronic Nonbacterial Osteomyelitis (CNO) is a rare auto-inflammatory disease that mainly affects children, and manifests with single or multiple painful bone lesions. Due to the lack of specific laboratory markers, CNO diagnosis is a matter of exclusion from different conditions, first and foremost bacterial osteomyelitis and malignancies. Whole Body Magnetic Resonance (WBMR) and bone biopsy are the gold standard for the diagnosis. Although the association with Inflammatory Bowel Disease (IBD) has been reported in the literature, cases of CNO in celiac patients have never been described before.

Case presentation: We report about a girl of 3 years and 8 months of age who presented with severe bone pain, slight increase of inflammatory markers, micro-hematuria and high calprotectin values. Her personal medical history was uneventful, apart from low weight growth. She had never complained of abdominal pain or other gastro-intestinal symptoms. WBMR showed the classical features of multifocal CNO, and biopsy confirmed the diagnosis. Celiac disease (CD) was suspected on the basis of antibody screening, and confirmed by gut biopsy. With gluten-free diet the patient achieved rapid and complete symptom remission together with healing of all the bone lesions proven by WBMR. Three years after the onset of the disease the girl is healthy and totally asymptomatic, still on clinical and radiological follow-up.

Conclusions: Based on our experience, the diagnostic work-up of new cases of CNO should include the screening test for CD and, according to the literature, the possibility of IBD should also be properly ruled out. When CNO and CD coexist, gluten-free diet, combined with antinflammatory therapy, could be able to completely reverse bone lesions, shortening the duration of medical treatment. Because the diseases' onset is seldom simultaneous, patients with CNO and IBD deserve a properly extended follow-up. Finally, the analysis of the relationship between CNO and autoimmune intestinal diseases provides a unique opportunity to understand the pathophysiological pro-inflammatory network underlying both types of disorders and it is necessary to make the most suitable therapeutic choice.

Keywords: Autoimmune intestinal diseases; Bone inflammation; Chronic nonbacterial osteomyelitis; Pediatrics.

Fig. 1

Pelvis MRI at disease onset. a The T2w sequence documents some areas of altered signal referable to spongious edema, some of them with symmetrical distribution, blurred, involving the limiting joints of the sacro-iliac synchondroses and more cranially the iliac crests, others with asymmetrical distribution, in the presence of conspicuous edematous alteration of the pre-symphyseal side of the right ileo- and ischio-pubic branches that on the opposite side seems only veiledly hinted at. b, c Changes are accompanied by discrete contrastographic impregnation in the CE-FS T1w sequence, particularly that located at the pubic site on the right, where concomitant periosteal reaction is seen, with traces of initial edema of the adjacent adductor muscle bundles

Fig. 2

Spine MR at disease onset. At the level of the lumbar vertebrae, symmetrical alterations with similar pre- (a STIR) and post-contrastographic (b T1w CE-FS) signal are reported at the level of the transverse processes of L5 and, more nuanced, at the antero-superior edge of L1 in the right paramedian location and at the lower portion of the soma of L2

Fig. 3

a, b, c WBMR four months after the gluten-free diet start. Almost complete resolution of the alterations described at the previous MRI examination. In particular, alterations previously located at the sacral flaps, iliac side of the synchondroses, iliac crests, right pubic spine, chondrocostal and sternal joints, distal clavicles and proximal humeri, distal metaphyses of radius and ulna, and acetabular roofs are no longer recognizable. Clear reduction of alterations at distal femoral and proximal tibial metaphyseal regions, where only a tinge of signal hyperintensity in STIR accompanied by a veiled T1 hypointensity remains, in the absence of significant alterations in diffusion sequences; at this level, the previously reported edematous perischelectric soft tissue alterations are no longer evident