Chronic Nonbacterial Osteomyelitis Research Articles

Clinical characteristics and predictors for recurrence in chronic nonbacterial osteomyelitis: a retrospective multicenter analysis.

Chronic nonbacterial osteomyelitis (CNO) is a rare disease of unknown etiology and most commonly occurs during childhood or adolescence. The purpose of this study is to collect data on the clinical features, outcomes, and management of the disease and to identify the factors affecting recurrence. This is a retrospective multicenter cross-sectional study of pediatric patients diagnosed with CNO. A total of 87 patients with a diagnosis of CNO followed for at least 6 months in 8 pediatric rheumatology centers across the country between January 2010 and December 2021 were included in this study. The study included 87 patients (38 girls, 49 boys; median age: 12.5 years). The median follow-up time was 20 months (IQR: 8.5-40). The median time of diagnostic delay was 9.9 months (IQR: 3-24). Arthralgia and bone pain were the most common presenting symptoms. Multifocal involvement was detected in 86.2% of the cases and a recurrent course was reported in one-third of those included in the study. The most commonly involved bones were the femur and tibia. Vertebrae and clavicles were affected in 19.5% and 20.6% of cases, respectively. The erythrocyte sedimentation rate (ESR) values of 60.9% of the patients were above 20 mm/h and the C-reactive protein values of 44.8% were above 5 mg/L. The remission rate was 13.3% in patients using nonsteroidal antiinflammatory drugs and 75.0% in those using biological drugs. Vertebral and mandibular involvement and high ESR values at the time of diagnosis were associated with recurrence. In this multicenter study, CNO with vertebral and mandibular involvement and high ESR at diagnosis were associated with recurrence.

Immunological Characterization of Chronic Nonbacterial Osteomyelitis (CNO) in Adults: A Cross-Sectional Exploratory Study.

Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features. CNO pathophysiology, including the key drivers of inflammation, remains largely unknown. For pediatric CNO, a role for pro-inflammatory cytokine dysregulation has been proposed, but studies in adults are scarce. We therefore provide immunological characterization of adult CNO. Cross-sectional study in our referral center including adult CNO patients (n = 172) and healthy controls (n = 65). Inflammation parameters and systemic inflammatory based scores(SIBS, including neutrophil/lymphocyte ratio [NLR] and systemic immune inflammation index [SII]) were compared between groups. Cytokine expression was explored with electrochemiluminescent immunoassays in 33 patients, eight healthy controls and 21 osteoporosis patients. Routine inflammation markers were higher in patients than in controls, but generally remained within reference range. Systemic inflammation was more pronounced in patients with additional vertebral involvement as compared to those osteitis in the anterior chest wall alone, in patients with comorbid pustulosis palmoplantaris or psoriasis, and in patients with strongly rather than moderately increased lesional uptake on nuclear imaging. SII was elevated in CNO patients too, but NLR was not. Cytokine expression was generally nondifferential between patients and both control groups, and patients displayed low absolute concentrations of pro-inflammatory cytokines. In this adult CNO cohort, systemic inflammation was generally subtle, but more pronounced in patients with vertebral lesions, associated skin disease, and strongly increased uptake on nuclear imaging. SII was increased in patients compared to healthy controls. Contrasting pediatric studies, we found no increased expression of the pro-inflammatory cytokines that have been proposed to drive the inflammatory cascade, like interleukin-6, -8, and -17 (IL-6, IL-8, and IL-17), and tumor necrosis α (TNF-α). Further studies are needed to evaluate the use of SII in diagnosis and monitoring of CNO, and elucidate the role of cytokine dysregulation in adult disease. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Chronic non-bacterial osteomyelitis and immune checkpoint molecules.

We aimed to investigate the plasma levels and cell surface expression of two checkpoint molecules, TIM-3 (T cell immunoglobulin and mucin domain-containing protein 3) and PD-1 (programmed cell death protein 1), in pediatric patients with chronic non-bacterial osteomyelitis (CNO). Plasma samples of CNO patients were collected at diagnosis or during biologic agent treatment. Plasma levels of TIM-3 and PD-1 were measured using the sandwich enzyme-linked immunosorbent assay method, and the expression of the two immune checkpoint molecules on the cell surface was analyzed by isolating peripheral blood mononuclear cells by density gradient centrifugation technique. Twenty-seven patients with CNO (14 boys, 51.9%) and six healthy controls (3 boys, 50%) were enrolled in the study. There were no age differences between CNO patients and healthy controls (median age 14.5 vs. 13.5 years, respectively, p=0.762). Of the CNO patients, 18 were included at the time of diagnosis while 9 were receiving biologic treatment at enrollment. The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls (p=0.011). However, no significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls (p=0.083 and p=0.245, respectively). There was also no statistically significant difference in plasma TIM-3 levels of the patient and control groups (p=0.981). CNO is an autoinflammatory disease, and overall, our results suggest that T cell exhaustion may not be significant in CNO. Further research is needed to find out whether the immune checkpoints are mainly associated with autoimmunity but not autoinflammation. Key Points • The median plasma PD-1 levels were significantly lower in the CNO group than in the healthy controls. • No significant difference was found in the cellular expression of PD-1 and TIM-3 on CD3+CD4+ T cells in patients and healthy controls. •Our results suggest that T cell exhaustion may not be significant inCNO pathogenesis.

OA02 Validation of newly proposed ACR/EULAR classification criteria for pediatric chronic nonbacterial osteomyelitis

Abstract Background Chronic nonbacterial osteomyelitis (CNO) is an aseptic autoinflammatory bone disease of unknown aetiology. This diagnosis can be delayed due to the non-specific nature of symptoms, referral patterns to non-rheumatology specialists and normal imaging studies. New ACR/EULAR classification criteria have been proposed for CNO and were presented at the American College of Rheumatology scientific meeting in 2022. This study seeks to validate these new classification criteria. Methods This is a retrospective case-series of paediatric patients diagnosed with CNO (n = 34). They were diagnosed and managed between 2012 and 2022 at the University of Virginia in Charlottesville, Virginia and Bon Secours Mercy Health in Richmond, Virginia. The entry criteria of chronic bone pain, age < 18 years, abnormal radiograph and/or MRI were used prior to applying the newly proposed ACR/EULAR classification criteria. Ten domains were evaluated to indicate whether a patient has CNO; those who scored 55 points or higher qualified (see table). The clinical manifestations, laboratory results, and imaging studies that lead to a diagnosis of CNO were reviewed in detail. We applied and validated the newly proposed classification criteria for CNO to this Virginia cohort of previously diagnosed paediatric CNO patients. We also reviewed the characteristics of those that did not fulfill these classification criteria. Result Upon application of the newly proposed ACR/EULAR classification criteria for CNO, 31 out of 34 patients (91%) were found to meet these classification criteria. Of the three patients diagnosed with CNO that did not fulfill the criteria, none had ‘least specific sites’ such as hands or neurocranium, all had elevated ESR and two out of three had an initial response to antibiotics. Their scores were 49, 51 and 53 with classification criteria being met with 55 or higher. The average age at diagnosis was 10 (range 2–17) years-old with the average time between onset of symptoms to confirmed radiographic evidence being 25 (range 1–120) months. The most common presenting symptoms were bone pain (100%) and arthritis (52%) with fever (23%) and rash (3%) being less common. Elevated ESR (39%) and CRP (39%) were found at initial visit with rheumatology. Evidence of commonly seen radiographic abnormalities leading to CNO diagnosis was found with regional MRI (65%), bone scan (42%) with some requiring full body MRI (26%) to confirm other lesions. Some patients did have multiple imaging studies including X-ray, CT, bone scan, MRI and bone biopsy in their workup. Conclusion This retrospective chart review validates the newly proposed ACR/EULAR classification criteria for CNO. We conclude that these criteria are easy to apply even in the absence of a bone biopsy or advanced imaging studies. This will aid in the development of a homogeneous cohort for future studies in CNO. Implication The newly proposed ACR/EULAR classification criteria can be easily applied to a cohort of CNO patients. These criteria have taken into account the lack of advanced imaging availability in certain institutions and lack of availability of a bone biopsy. Our work is ethically approved.

Diagnostic and therapeutic practices in adult chronic nonbacterial osteomyelitis (CNO)

BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.MethodsA primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.Results36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2–3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments.ConclusionsFollowing from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.

Treatment of Chronic Nonbacterial Osteomyelitis with Bisphosphonates.

Treatment of Chronic Nonbacterial Osteomyelitis with Bisphosphonates.

Update on treatment responses and outcome measure development in chronic nonbacterial osteomyelitis.

To review recent trends in treatment and recent progress in developing outcome measures needed for chronic nonbacterial osteomyelitis (CNO) clinical trials. CNO is an autoinflammatory bone disease. In a minority of patients, the disease is genetically driven, and diagnosis can be made by DNA sequencing. However, for nonsyndromic CNO there is no diagnostic test. The number of children with CNO appears to be increasing and damage is common. Increases in CNO diagnosis is due to raised awareness, increased availability of whole-body magnetic resonance imaging and rising incidence. Treatment remains empiric and it is unclear which second line treatment is superior. Tumor necrosis factor inhibitors (TNFi) and bisphosphonates continue to be used as second line agents for nonsteroidal anti-inflammatory drugs (NSAID) refractory CNO; newer immune modulatory medications are used if this fails. Validated classification criteria, clinical outcome measures and imaging scoring standards are needed for successful clinical trials. Best treatment for NSAID refractory CNO remains unclear. Classification criteria, clinical outcomes measures and standardized imaging scoring have been developed or are near completion. This will facilitate robust clinical trials in CNO with the goal of having approved medications for this painful disease.

Chronic non-bacterial osteomyelitis with autoimmune hepatitis: a case report and literature review

Objective: To summarize the clinical characteristics and treatments of chronic non-bacterial osteomyelitis with autoimmune hepatitis in children. Methods: A child who had chronic non-bacterial osteomyelitis with autoimmune hepatitis was admitted to the Department of Gastroenterology of the Children's Hospital Capital Institute of Pediatrics at April 2022. The clinical data was retrospectively analyzed. Using the keywords of "chronic non-bacterial osteomyelitis""autoimmune hepatitis" in Chinese and English, the literature from database establishment to December 2022 in CNKI, Wanfang, China Biomedical Literature Database and Pubmed was searched. Combined with this case, the clinical characteristics and treatment of chronic non-bacterial osteomyelitis combined with autoimmune hepatitis were analyzed. Results: A 5 years and 3 months girl was admitted to the Department of Gastroenterology of Children's Hospital, Capital Institute of Pediatrics for "transaminase elevated for 1 year and swelling of right maxillofacial area for half a year". The physical examinations at admission found a 4.0 cm × 4.0 cm swelling area with tenderness before the right ear, abdominal distention with visible abdominal wall vein, firm and enlarged liver (10.0 cm below the xiphoid and 4.5 cm below the right ribs), and splenomegaly (Line Ⅰ 10.0 cm, Line Ⅱ 11.5 cm, and Line Ⅲ 25.0 cm). There was no redness, swelling or restriction of the limbs. Laboratory examination found abnormal liver function with alanine aminotransferase 118 U/L, aspartate aminotransferase 227 U/L, γ-glutamyltransferase 360 U/L, and positive direct anti-human globulin test; immunology test found immunoglobulin G 41.60 g/L and a homogeneous type of antinuclear antibody of 1∶1 000; the autoimmune hepatitis antibody test found a positive anti-smooth muscle antibody (1∶100). Liver biopsy showed moderate interfacial inflammation and the patient was diagnosed with autoimmune hepatitis (International Autoimmune Hepatitis Group 19). The imaging findings showed extensive involvement of the bilateral mandible, while the right side was severe. There were expansile bone changes, thinning of the bone cortex, and significant swelling of the surrounding soft tissue in the mandibular body, mandibular angle, and mandibular ramus. After treatment of glucocorticoid, the swelling of the right maxillofacial region disappeared and the transaminase returned to normal. Only one case was reported before in English and none in Chinese. The two cases were both girls whose main clinical features were joint pain and swelling. The previous case started with pain in both knee joints, and developed liver injury during treatment while this case had liver injury as the initial clinical presentation. Besides, the affected sites and degrees of arthritis in the 2 cases were different. After glucocorticoid treatment, the clinical symptoms were alleviated, and transaminases returned to normal. Conclusions: Chronic non bacterial osteomyelitis may involve the liver and manifest as autoimmune hepatitis. Glucocorticoids therapy is effective.

Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis.

Prospective comparative effectiveness research (CER) in chronic nonbacterial osteomyelitis (CNO) is lacking. Our objectives were to (1) determine the use and safety of each consensus treatment plan (CTP) regimen for CNO, (2) assess the feasibility of using the Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) data for CER, and (3) develop and validate a CNO clinical disease activity score (CDAS) using CHOIR. Consenting children or young adults with CNO were enrolled into CHOIR. Demographic, clinical, and imaging data were prospectively collected. The CNO CDAS was developed through a Delphi survey and nominal group technique. External validation surveys were administered to CHOIR participants. One hundred forty (78.2%) CHOIR participants enrolled between August 2018 and September 2020 received at least 1 CTP regimen. Baseline characteristics from different CTP groups were well matched. Patient pain, patient global assessment, and clinical CNO lesion count were key variables included in the CNO CDAS. The CDAS showed a strong correlation with patient/parent report of difficulty using a limb, back, or jaw and patient/parent report of disease severity, but a weak correlation with patient/parent report of fatigue, sadness, and worry. The change in CDAS was significant in patients reporting disease worsening or improvement (P < 0.001). The CDAS significantly decreased after initiating second-line treatments from median 12.0 (IQR 8.0-15.5) to 5.0 (IQR 3.0-12.0; P = 0.002). Although second-line treatments were well tolerated, psoriasis was the most common adverse event. The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER.

Priorities in Chronic nonbacterial osteomyelitis (CNO) – results from an international survey and roundtable discussions

ObjectiveChronic 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.MethodsA 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).ResultsResponses 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.ConclusionsAgreement 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.

HLA-B*27 is associated with CNO in a European cohort

ObjectivesTo determine the influence of HLA-B27 positivity on risk of developing chronic nonbacterial osteomyelitis (CNO).MethodsHLA-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.ResultsHLA-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.ConclusionCarriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases.

Pediatric autoinflammatory bone disorders-a mini review with special focus on pathogenesis and inborn errors of immunity.

Autoinflammatory bone disorders are a group of diseases characterized by sterile osteomyelitis. This includes chronic nonbacterial osteomyelitis and the monogenic forms, Majeed syndrome and deficiency of the interleukin-1 receptor antagonist. These disorders result from innate immune system dysregulation and cytokine imbalance that triggers inflammasome activation causing downstream osteoclastogenesis and excessive bone remodeling. In this review, we will summarize the immunopathogenesis of pediatric autoinflammatory bone diseases with a special focus on the genetics and inborn errors of immunity, while briefly touching on the clinical manifestations and management of each disease as well as areas for future research.

Chronic non-bacterial osteomyelitis in SAPHO syndrome complicated by subclavian vein obstruction.

Chronic non-bacterial osteomyelitis in SAPHO syndrome complicated by subclavian vein obstruction.

MRI features of spinal chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis in children.

Spinal lesions in pediatric chronic recurrent multifocal osteomyelitis/chronic non-bacterial osteomyelitis (CRMO/CNO) can cause permanent sequelae; thus, early recognition of these is vital for management. To characterize the MR imaging features and patterns of pediatric spinal CRMO/CNO. This cross-section study received IRB approval. The first available MRI with documented spine involvement in children with CRMO/CNO was reviewed by a pediatric radiologist. Descriptive statistics were used to describe the characteristics of vertebral lesions, disc involvement, and soft tissue abnormality. Forty-two patients were included (F:M, 30:12); median age was 10years (range 4-17). At diagnosis, 34/42 (81%) had spine involvement. Kyphosis in 9/42 (21%) and scoliosis in 4/42 (9.5%) patients were present at the time of spinal disease recognition. Vertebral involvement was multifocal in 25/42 (59.5%). Disc involvement was found in 11/42 (26%) patients, commonly in the thoracic spine and often with adjacent vertebrae height loss. Posterior element abnormalities were present in 18/42 patients (43%) and soft tissue involvement in 7/42 (17%). One hundred nineteen vertebrae were affected, commonly the thoracic vertebrae (69/119; 58%). Vertebral body edema was focal in 77/119 (65%) and frequently superior (42/77; 54%). Sclerosis and endplate abnormality were present in 15/119 (13%) and 31/119 (26%) vertebrae, respectively. Height loss was present in 41/119 (34%). Chronic non-bacterial osteomyelitis of spine is usually thoracic. Vertebral body edema is often focal at the superior vertebral body. Kyphosis and scoliosis occur in a quarter and vertebral height loss in a third of children at spinal disease recognition.

Gathering expert consensus to inform a proposed trial in chronic nonbacterial osteomyelitis (CNO)

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that primarily affects children and adolescents. CNO is associated with pain, bone swelling, deformity, and fractures. Its pathophysiology is characterized by increased inflammasome assembly and imbalanced expression of cytokines. Treatment is currently based on personal experience, case series and resulting expert recommendations.Randomized controlled trials (RCTs) have not been initiated because of the rarity of CNO, expired patent protection of some medications, and the absence of agreed outcome measures. An international group of fourteen CNO experts and two patient/parent representatives was assembled to generate consensus to inform and conduct future RCTs.The exercise delivered consensus inclusion and exclusion criteria, patent protected (excludes TNF inhibitors) treatments of immediate interest (biological DMARDs targeting IL-1 and IL-17), primary (improvement of pain; physician global assessment) and secondary endpoints (improved MRI; improved PedCNO score which includes physician and patient global scores) for future RCTs in CNO.

Transcriptome analysis based on machine learning reveals a role for autoinflammatory genes of chronic nonbacterial osteomyelitis (CNO)

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder. The origin and development of CNO involve many complex immune processes, resulting in delayed diagnosis and a lack of effective treatment. Although bioinformatics analysis has been utilized to seek key genes and pathways in CNO, only a few bioinformatics studies that focus on CNO pathogenesis and mechanisms have been reported. This study aimed to identify key biomarkers that could serve as early diagnostic or therapeutic markers for CNO. Two RNA-seq datasets (GSE133378 and GSE187429) were obtained from the Gene Expression Omnibus (GEO). Weighted gene coexpression network analysis (WGCNA) and differentially expressed gene (DEG) analysis were conducted to identify the genes associated with CNO. Then, the autoinflammatory genes most associated with CNO were identified based on the GeneCards database and a CNO prediction model, which was created by the LASSO machine learning algorithm. The accuracy of the model and effects of the autoinflammatory genes according to receiver operating characteristic (ROC) curves were verified in external datasets (GSE7014). Finally, we performed clustering analysis with ConsensusClusterPlus. In total, eighty CNO-related genes were identified and were significantly enriched in the biological processes regulation of actin filament organization, cell–cell junction organization and gamma-catenin binding. The main enriched pathways were adherens junctions, viral carcinogenesis and systemic lupus erythematosus. Two autoinflammatory genes with high expression in CNO samples were identified by combining an optimal machine learning algorithm (LASSO) with the GeneCards database. An external validation dataset (GSE187429) was utilized for ROC analysis of the prediction model and two genes, and the results indicated good efficiency. Then, based on consensus clustering analysis, we found that the expression of UTS2 and MPO differed between clusters. Finally, the ceRNA network of lncRNAs and the small molecule compounds targeting the two autoinflammatory genes were predicted. The identification of two autoinflammatory genes, the HCG18/has-mir-147a/UTS2/MPO axis and signalling pathways in this study can help us understand the molecular mechanism of CNO formation and provides candidate targets for the diagnosis and treatment of CNO.

Diagnosis and Treatment of Chronic Non-bacterial Osteomyelitis: A Survey on Current Practices Adopted by Pediatric Rheumatologists in Saudi Arabia.

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease usually managed by pediatric rheumatologists (PRs). There is a need for a consensus treatment plan to minimize the diversity in clinical practice in the diagnosis and management of CNO. In this study, we explored the practice of PRs in Saudi Arabia on the diagnosis and treatment of patients with CNO. This is a cross-sectional study that was conducted among PRs in Saudi Arabia (May to September 2020). A survey was performed among PRs registered in the Saudi Commission for Health Specialties using an electronic-based questionnaire. The survey consisted of 35 closed-ended questions about the diagnosis and management of CNO patients. We explored the approaches adopted by PRs in diagnosing and monitoring the disease activity, their awareness of clinical possibilities that necessitate ordering bone biopsy, and the treatment choices they considered for CNO patients. We scrutinized data from a total of 77% (n=41/53) PRs who responded to our survey. Magnetic resonance imaging (MRI) was reported as the most frequently used modality in suspected CNO (82%, n=27/33), followed by plain X-ray (61%) and bone scintigraphy (58%). Magnetic resonance imaging of a symptomatic site is the imaging modality of choice for the diagnosis of CNO (82%), Followed by X-ray (61%) and bone scintigraphy (58%). The reasons for performing bone biopsy were unifocal lesions (82%), unusual sites of presentation (79%), and multifocal lesions (30%). The preferred treatment regimens were bisphosphonates (53%), non-steroidal anti-inflammatory drugs alone (43%), or biologics with bisphosphonates (28%). The reasons to upgrade the treatment in CNO included the development of vertebral lesions (91%), the development of new lesions in MRI (73%), and the elevation of inflammatory markers (55%). The disease activity was assessed by history and physical examination (91%), inflammatory markers (84%), MRI of targeted symptomatic site (66%), and a whole-body MRI (41%). The approach todiagnosis and treatment of CNO varies among PRs in Saudi Arabia. Our findings provide a background for the development of a consensus treatment plan for challenging CNO patients.

Retrospective Analysis of Children with Chronic Non-bacterial Osteomyelitis

Retrospective Analysis of Children with Chronic Non-bacterial Osteomyelitis

Experience of successful treatment of a patient with chronic non-bacterial osteomyelitis (clinical case)

BACKGROUND: Chronic nonbacterial osteomyelitis is a rare autoinflammatory bone disease with periods of relapses and remissions. No etiotropic therapy, diagnostic and treatment standards exist, patients are observed by rheumatologists, immunologists, and orthopedist. They receive symptomatic, anti-inflammatory treatment, broad-spectrum antibiotics, immunosuppressants to control inflammation, which helps to prevent new or to reduce existing pathological foci.&#x0D; CLINICAL CASE DESCRIPTION: This article describes the effect of immune therapy and osteotropic treatment with zoledronic acid combination in a patient with chronic non-bacterial osteomyelitis. In a clinical observation involving comprehensive examination, including radiological (radiography, computed tomography and magnetic resonance imaging) and laboratory methods, a positive outcome was achieved using conservative methods of treatment in a patient with chronic non-bacterial sternum osteomyelitis.&#x0D; CONCLUSION: Thus, a combination of bisphosphonates and immunotherapy may be promising in the treatment of chronic non-bacterial osteomyelitis. However, it is unknown as to how long the remission will last and what treatment program is necessary for the final disease resolution.

Childhood-Onset Sacroiliitis: Causes and Correlation Between Clinical Findings and Magnetic Resonance Imaging.

The aims of this study were to describe disease associations of magnetic resonance imaging (MRI)-confirmed and clinically symptomatic sacroiliitis in pediatric patients with rheumatic diseases and to examine the relationship between patient characteristics and MRI findings of the sacroiliac joint (SIJ). Demographic and clinical data were extracted from the electronic medical records of the patients with sacroiliitis followed in the last 5 years. Active inflammatory and structural damage lesions of the SIJ-MRI were examined by the modified Spondyloarthritis Research Consortium of Canada scoring system, and correlation analysis of these results with clinical characteristics was evaluated. A total of 46 symptomatic patients were found to have MRI-proven sacroiliitis of 3 different etiologies: juvenile idiopathic arthritis (JIA) (n = 17), familial Mediterranean fever (FMF) (n = 14), and chronic nonbacterial osteomyelitis (CNO) (n = 8). Seven patients, FMF and JIA (n = 6) and FMF and CNO (n = 1), had a co-diagnosis that might cause sacroiliitis. Although inflammation scores and structural damage lesions did not statistically differ between the groups, capsulitis and enthesitis on the MRI were more frequently detected in the CNO group. There was a negative correlation between symptom onset and inflammation scores of bone marrow edema. Disease composite scores and acute phase reactants were correlated with MRI inflammation scores. We demonstrated that JIA, FMF, and CNO were the major rheumatic causes of sacroiliitis in children originating from the Mediterranean region. Quantitative MRI scoring tools can be used to assess the inflammation and damage of the SIJ in rheumatic diseases, show discrepancies between them, and have an important correlation with various clinical and laboratory features.