Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn\'s disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Spinal involvement by chronic non-bacterial osteomyelitis (CNO) has been increasingly reported in recent years, often being presented as a diagnostic dilemma requiring differential diagnosis with bacterial spondylodiscitis and/or neoplasia. This study was aimed at identifying the imaging features of CNO facilitating its differentiation from other spinal diseases. Two radiologists assessed the imaging studies of 45 patients (16 male and 29 female, aged from 6 to 75 years, 15 children) with CNO collected from 5 referential centers. Spinal lesions were found in 17 patients (2 children and 15 adults), most often in the thoracic spine. In children, the lesions involved short segments with a destruction of vertebral bodies. In adults, the main findings were prominent bone marrow edema and osteosclerosis, endplate irregularities, and ankylosing lesions extending over long segments; paraspinal inflammation was mild and abscesses were not observed. In both children and adults, the involvement of posterior elements (costovertebral and facet joints) emerged as an important discriminator between CNO and neoplasia/other inflammatory conditions. In conclusion, a careful inspection of imaging studies may help to reduce the number of biopsies performed in the diagnostic process of CNO.

We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient\'s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder that predominantly affects children and young people. The pathophysiology and molecular mechanisms of CNO remain poorly understood, and diagnostic criteria and biomarkers are lacking. As a result, treatment is empiric and follows personal experience, case series and expert consensus plans.
METHODS: A survey was designed to gain insight on clinician and patient experiences of diagnosing and treating CNO and to collate opinions on research priorities. A version containing 24 questions was circulated among international expert clinicians and clinical academics (27 contacted, 21 responses). An equivalent questionnaire containing 20 questions was shared to explore the experience and priorities of CNO patients and family members (93 responses).
RESULTS: Responses were used to select topics for four moderated roundtable discussions at the \"International Conference on CNO and autoinflammatory bone disease\" (Liverpool, United Kingdom, May 25-26th, 2022). The group identified deciphering the pathophysiology of CNO to be the highest priority, followed by clinical trials, necessary outcome measures and classification criteria. Surprisingly, mental wellbeing scored behind these items.
CONCLUSIONS: Agreement exists among clinicians, academics, patients and families that deciphering the pathophysiology of CNO is of highest priority to inform clinical trials that will allow for the approval of medications for the treatment of CNO by regulatory agencies.

Juvenile idiopathic arthritis (JIA) is a collective term for pediatric inflammatory arthritis of unknown etiology, which presents diverse clinical and imaging findings. The pathogenesis is complex; however, most cases stem from an autoimmune mechanism. Herein we provide a short review of imaging findings of JIA. Imaging assessment begins with plain radiography demonstrating joint swelling, periarticular osteopenia, and juxtaarticular bone erosion. Bone erosion occurs later in JIA. Instead, aberrant epimetaphyseal growth often gives the first clue to the diagnosis. US and MRI can demonstrate the details of the synovium, cartilage, and subchondral bone. JIA is subdivided into oligoarthritis, polyarthritis (rheumatoid factor-negative and positive), psoriatic arthritis, enthesitis-related arthritis, and systemic JIA. Awareness of the different clinical characteristics, pathogenic background, and prognosis of each subtype facilitates a more advanced, imaging-based diagnosis. Unlike the other types, systemic JIA is an autoinflammatory disease accompanied by inflammatory cytokinemia and systemic symptoms stemming from aberrant activation of the innate immunity. Other autoinflammatory diseases, both monogenic (e.g., NOMID/CINCA) and multifactorial (e.g., CRMO), are also discussed.

OBJECTIVE: To determine the influence of HLA-B27 positivity on risk of developing chronic nonbacterial osteomyelitis (CNO).
METHODS: HLA-B*27 genotype was assessed in 3 European CNO populations and compared with local control populations (572 cases, 33,256 controls). Regional or whole-body MRI was performed at diagnosis and follow-up in all cases which reduces the risk of disease misclassification. Genotyping was performed using either next generation DNA sequencing or PCR based molecular typing. Statistical analysis used Fisher\'s exact test with Bonferroni correction and a fixed effects model for meta-analysis of odds ratios.
RESULTS: HLA-B*27 frequency was higher in all 3 populations compared with local controls (combined odds ratio (OR) = 2.2, p-value = 3 × 10-11). This association was much stronger in male compared with female cases (OR = 1.99, corrected p-value = 0.015). However, the HLA-B*27 status was not statistically significantly associated with co-occurrence of psoriasis, arthritis or inflammatory bowel disease.
CONCLUSIONS: Carriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases.

A 16-year-old girl with a history of clavicular chronic recurrent multifocal osteomyelitis (CRMO) presented with fever, vomiting, urinary and bowel retention, thigh paresthesia, and back pain for 2 days. The patient had 2 separate viral illnesses within a month prior to presentation. Spine magnetic resonance imaging (MRI) displayed increased T2 hyperintensity of the central grey matter from C3 to the conus medullaris (Figure 1). Findings were consistent with longitudinally extensive transverse myelitis. Cerebrospinal fluid analysis revealed elevated protein (51; reference range: <48 mg/dL), IgG index (.74; reference range <.70), and glucose (99; reference range 40-75 mg/dL). There was pleocytosis of 22 white blood cells (88% lymphocytes and 12% monocytes) with negative AQP4 and MOG antibodies. COVID-19 spike protein was positive with a negative PCR and non-immunized status, suggesting prior infection. Four months later, a pelvic MRI revealed new evidence of CRMO.

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is a rare chronic autoinflammatory disorder of unknown etiology. Radiological investigation, including the use of magnetic resonance imaging and nuclear medicine is pivotal to the diagnosis of SAPHO syndrome. We present a case of a 15-year-old male diagnosed with SAPHO syndrome displaying the classic diagnostic findings of this condition on bone scan and magnetic resonance imaging.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disease for which a lack of bacterial involvement is a key diagnostic feature to distinguish it from other symptomatically related diseases. However, the growing evidence suggesting an involvement of the host-associated microbiota in rheumatic disorders together with the now wide accessibility of modern culture-independent methods warrant a closer examination of CRMO.
In this study, we show through bacterial 16S rRNA gene profiling that numerous features of the oral- and fecal microbial communities differentiate children with and without CRMO.
Notably, communities in diseased children are characterized by a lack of potential probiotic bacteria in the fecal community and an overabundance of known pathobionts in the oral microbial communities. Of special interest is the HACEK group, a set of commonly known oral pathogens that are implicated in the development of several acute and chronic diseases such as osteitis and rheumatoid arthritis. Furthermore, we observe that gut bacterial communities in the diseased children appear to reflect an altered host physiology more strongly than the oral community, which could suggest an oral disease origin followed by propagation and/or responses beyond the oral cavity.
Bacterial communities, in particular the oral microbiota, may serve as an indicator of underlying susceptibility to CRMO, or play a yet undefined role in its development.

Chronic recurrent multifocal osteomyelitis (CRMO) is aseptic and can be diagnosed by excluding other diseases, such as bacterial osteomyelitis, scurvy, metabolic disorders, and malignant diseases; therefore, bone biopsy is usually performed to confirm the diagnosis. To prevent misdiagnosis, the appropriate timing and location for biopsy should be determined from an active phase of inflammation. We presented 3 cases of CRMO involving the mandible: Case 1: A 2-year-old girl diagnosed with CRMO in the chronic phase. A sonogram showed a slightly low echoic area adjacent to the bone cortex. Pathological examination revealed a slight accumulation of leukocytes and plasma cells, as well as predominant fibrous stroma. Case 2: A 9-year-old girl diagnosed with CRMO with massive new osteoid formation. A sonogram showed a massive inhomogeneous low echoic area adjacent to the bone cortex. Pathological examination revealed massive osteoid formation and scattered inflammatory cells infiltration. Case 3: A 3-year-old girl diagnosed with CRMO in the active phase. A sonogram showed a massive hypoechoic area adjacent to the bone cortex and hyperechogenicity associated with a muscular and subcutaneous edema. Pathological examination revealed massive bone destruction and neutrophils infiltration within damaged osteoid. Ultrasound was able to visualize the degree of inflammation in the mandible corresponding to that of the surrounding soft tissue in all 3 cases. Therefore, ultrasound would be useful in determining the appropriate timing and location for bone biopsy.