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Bone marrow is a highly cellular tissue undergoing significant developmental and physiologic changes with age. Indeed, with maturation from pediatric to the adult age there is a progressive, centrifugal conversion from red to yellow bone marrow. Histological characteristics of bone marrow are reflected in MR image signal. MR is therefore extremely sensitive in detecting pathological changes which are mostly characterized by increased free water causing high signal intensity on T2. Among the numerous diseases causing bone marrow edema in children chronic nonbacterial osteomyelitis (CNO) certainly has to be mentioned. This idiopathic inflammatory disorder is characterized by nonspecific migrating symptoms like skeletal pain with phases of exacerbations and relapses with alternating acute and chronic MR signs and it is often a diagnosis of exclusion. Hence, with bone marrow edema, various features at imaging should be considered to differentiate malignancies such as osseous lymphoma, osteosarcoma, and Ewing's sarcoma as well as benign lesions like osteomyelitis, post-traumatic, or post-treatment bone marrow edema. The aim of this review is to recall the main characteristics of CNO and provide an overview of its main mimickers highlighting similarities and differences. [ABSTRACT FROM AUTHOR]

Objectives Extra-osseous (EO) manifestations are poorly characterized in chronic recurrent multifocal osteomyelitis (CRMO). This study aimed to further define the frequency, characteristics and treatment of EO events in CRMO and whether different phenotypes can be distinguished and benefit from special management. Methods This multicentre retrospective study included CRMO patients followed in several paediatric rheumatology departments in France between 2015 and 2022. EO manifestations were defined as skin lesions, gastrointestinal manifestations, arthritis, enthesitis, sacroiliitis, uveitis, vasculitis and fever. At the last visit, the physician defined CRMO as active in the presence of clinical manifestations including both osseous and EO symptoms. Results We included 133 patients; 87 (65.4%) were girls and the median age at first symptoms was 9.0 years (interquartile range 7.0–10.0). EO manifestations were described in 90 (67.7%) patients, with a predominance of skin lesions [ n  = 51/90 (56.7%)], followed by sacroiliitis [ n  = 38/90 (42.2%)], enthesitis [ n  = 21/90 (23.3%)], arthritis [ n  = 14/90 (15.6%)] and gastrointestinal manifestations [ n  = 6/90 (6.7%)]. The use of non-steroidal anti-inflammatory drugs and bisphosphonates did not differ by the presence or not of EO manifestations. Biologics were taken more frequently by patients with than without EO manifestations (P  < 0.001); TNF inhibitors were used in 33 (36.7%) EO-positive patients. Under this treatment, 18 (54.5%) patients achieved complete remission of osseous and EO manifestations. At the last visit, more EO+ than EO− patients were on treatment (P  = 0.009), with active disease in 58 (64.4%) patients. Conclusion The analysis of EO manifestations in CRMO delineates two groups of patients in terms of severity and treatments used. Our study opens up new pathophysiological leads that may underlie the wide range of CRMO phenotypes. [ABSTRACT FROM AUTHOR]

Background and Objectives: The diagnosis of rheumatic diseases in children is challenging and requires the use of advanced imaging examinations such as whole-body magnetic resonance imaging (MRI). Whole-body MRI allows visualization of bone marrow edema (BME), muscle edema, joint effusion and changes in the soft tissues surrounding the joints. The aim of this study was to collect and compare whole-body MRI findings, laboratory results and clinical manifestations of pediatric patients with suspected rheumatic disease. Materials and methods: In this retrospective single-center study, 33 patients who underwent whole-body MRI were included. Their age ranged from 9 to 17 years, and 24 (72.73%) of the patients were female. Patients were diagnosed as follows: juvenile idiopathic arthritis (27.27%), juvenile idiopathic inflammatory myopathies (21.21%), chronic nonbacterial osteomyelitis (21.21%) and other medical conditions (30.30%), such as arthritis associated with infection, scleroderma, Takayasu arteritis, polyarteritis nodosa and joint damage. Results: The most common symptom reported by 26 (79.79%) patients was pain. On physical examination, the limitation of joint mobility was examined in 17 (51.51%), swelling of the joints was observed in 12 (36.36%) patients and decreased muscle strength was noticed in 11 (33.33%) patients. An increase in the C-reactive protein (12%), erythrocyte sedimentation rate (9%), leukocyte count (9%) and creatine kinase (CK) (18%) was observed. Whole-body MRI revealed myositis (30%), joint effusion (27%) and BME (24%). The statistical analysis showed a significant relationship between myositis and the elevated CK level (p < 0.05). Conclusions: The most common symptom in the studied population was pain, while the limitation of joint mobility was found in more than half of patients. Myositis was the most commonly imaged lesion on the whole-body MRI and it was related to an increase in the CK level. [ABSTRACT FROM AUTHOR]

Objective: To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO). Methods: Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15 years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study. Results: Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2 years; age at diagnosis, 10.3 ± 3.3 years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%). Conclusion: Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis. Clinical relevance statement: When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible. Key Points: • Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected. [ABSTRACT FROM AUTHOR]

Introduction: chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder, that most commonly first appears in childhood. Symptoms can be nonspecific at first (fever, night sweats, fatigue), followed by bone pain, bone swelling, nocturnal pain, and impaired function of the affected part of the body. Diagnosis is usually delayed, because there are no widely accepted criteria for CNO, so differentialdiagnoses need to be excluded (malignancy, infection). It can be accompanied by severe complications (vertebral fractures). Case report: this case series presents three female patients who were diagnosed with chronic nonbacterial osteomyelitis. They were referred to a pediatric rheumatologist a minimum of eight months after the first symptoms occurred. The most frequent symptoms were nocturnal bone pain and swelling. None of the patients had a fever. The bones primarily affected were the clavicle, mandible, humerus and vertebra with secondary complications such as compressive vertebral fractures, and scoliosis. One developed paradoxical psoriasis while being treated with TNF inhibitors. Conclusion: this case report highlights the importance of considering chronic nonbacterial osteomyelitis as a potential cause of bone swelling and pain. The key factors for improving the outcome of patients with CNO are early recognition and timely treatment, as well as a multidisciplinary approach due to the complexity of the diagnosis. [ABSTRACT FROM AUTHOR]

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21–41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41–64) of patients displayed central sensitization on CSI, 61% (50–72) screened positive for fibromyalgia on FiRST and 14% (7–23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4–5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach. [ABSTRACT FROM AUTHOR]

Purpose: Primary chronic osteomyelitis (PCO) of the jaw is a non-infectious, inflammatory state of the jawbone of unknown etiology. This study aimed to investigate the occurrence of PCO in Sweden between the years 2012 and 2018, the characteristics of the condition, treatment methods, and outcomes. Material and methods: The search for patients with PCO in Sweden 2012–2018 was performed at 24 oral and maxillofacial surgery units in Sweden. Results: During this 6-year period, 17 patients were identified as diagnosed with PCO in Sweden. The mean age was 10.6 years at diagnosis, and the female:male ratio was 4:1. Conclusion: We conclude that PCO is a very rare disease in Sweden, and that standardized, well-defined criteria are necessary to calculate incidence rates but also to increase knowledge about etiology, clinical characteristics, and treatment outcomes in rare conditions such as PCO.

Abstract Introduction Chronic non-bacterial osteomyelitis (CNO) is a rare, non-infection- related inflammatory disorder that affects children and teens. Clinical manifestations of CNO range widely from moderate, time-limited, monofocal inflammation of the bone to extreme multifocal or chronically active inflammation of the bone. Objectives The main aim of this study was to explore the correlation between musculoskeletal (MSK) symptoms and health-related quality of life (HRQoL) in patients with CNO. Methods Children and adults with CNO and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical and therapeutic data, MSK discomfort form based on the Nordic MSK Questionnaire and HRQoL based on Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL rheumatology module. The inclusion criteria included diagnosis of CNO before the age of 18. Patients who had malignancies or any chronic rheumatic, MSK, neurological disease prior to CNO onset were excluded. Results There was a total of 68 participants, mostly females (66.2%), with median age 14 years and median disease duration 4.75 years. The median number of bones affected by CNO was 5 and ranged from 1 to 24 bones. Among the studied patients, 45 patients (66.2%) had MSK manifestations at the last month. The most commonly affected part was ankle and feet (26.5%). Regarding HRQoL, patients with MSK manifestations had lower scores than did patients without in PedsQL-4 (p

Objective: The aim of this study was to investigate the use of whole-body magnetic resonance imaging (WBMRI) in cases where we suspected rheumatic disease in our pediatric rheumatology clinic. Materials and Methods: We conducted a retrospective analysis of demographic, clinical, laboratory, and imaging data pertaining to pediatric patients who presented at our clinic and underwent WBMRI over the last 5 years. Our investigation targeted children experiencing diffuse musculoskeletal pain, where precise localization was challenging and suspicion of rheumatological pathology persisted despite inconclusive results from conventional diagnostic modalities. Results: A total of 87 patients (33 female) underwent WBMRI at our clinic, with a median age (minimum–maximum) of 11.3 (0.5-18) years. Whole-body magnetic resonance imaging was performed in 4 patients suspected with dermatomyositis (DM) where muscle biopsy was not feasible, revealing muscle involvement and myositis. Additionally, WBMRI was utilized in 4 patients diagnosed with chronic nonbacterial osteomyelitis (CNO) to assess recurrence, identifying new active lesions in 3 patients. Among the remaining 79 patients, 34 received a new diagnosis of CNO. Clinically, supported by additional findings in laboratory and WBMRI, 18 were diagnosed with juvenile idiopathic arthritis (JIA), 5 with protracted febrile myalgia syndrome (PFMS), 5 with acute osteomyelitis, and 1 with viral myositis. The results were normal for 17 patients. Conclusion: Most of the WBMRIs conducted at the clinic under study were primarily performed on patients suspected of having CNO. Additionally, WBMRI was found to be supportive and beneficial in cases of suspected DM, PFMS, and JIA during the diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: Chronic non-bacterial osteomyelitis (CNO) is a rare, non-infection- related inflammatory disorder that affects children and teens. Clinical manifestations of CNO range widely from moderate, time-limited, monofocal inflammation of the bone to extreme multifocal or chronically active inflammation of the bone. Objectives: The main aim of this study was to explore the correlation between musculoskeletal (MSK) symptoms and health-related quality of life (HRQoL) in patients with CNO. Methods: Children and adults with CNO and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical and therapeutic data, MSK discomfort form based on the Nordic MSK Questionnaire and HRQoL based on Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL rheumatology module. The inclusion criteria included diagnosis of CNO before the age of 18. Patients who had malignancies or any chronic rheumatic, MSK, neurological disease prior to CNO onset were excluded. Results: There was a total of 68 participants, mostly females (66.2%), with median age 14 years and median disease duration 4.75 years. The median number of bones affected by CNO was 5 and ranged from 1 to 24 bones. Among the studied patients, 45 patients (66.2%) had MSK manifestations at the last month. The most commonly affected part was ankle and feet (26.5%). Regarding HRQoL, patients with MSK manifestations had lower scores than did patients without in PedsQL-4 (p < 0.001) including domains of physical functioning (p < 0.001), emotional functioning (p = 0.033), social functioning (p < 0.001) and school functioning (p = 0.007) in addition to lower scores in PedsQL rheumatology module (p < 0.001) including domains of pain and hurt (p < 0.001), daily activities (p < 0.001), treatment (p = 0.035), worry (p = 0.001) and communication (p < 0.001). Conclusion: MSK manifestations have a negative impact on HRQoL in CNO patients. So, early identification and treatment are highly recommended. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Introduction Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone-disease of unknown origin. The National Pediatric Rheumatologic Database (NPRD) collects long-term data of children and adolescents with rheumatic diseases including CNO. Objective To assess characteristics, courses, and outcomes of CNO with onset in childhood and adolescence and to identify outcome predictors. Methods From 2015 to 2021 patients with a confirmed diagnosis of CNO, who were registered in the NPRD during their first year of disease and at least one follow-up visit, were included in this analysis and observed for up to 4 years. Results Four hundred patients with recent diagnosis of CNO were enrolled in the NRPD during the study period. After 4 years, patient data documentation was sufficient to be analyzed in 81 patients. A significant decline of clinical and radiological lesions is reported: at inclusion in the registry, the mean number of clinical lesions was 2.0 and 3.0 MRI lesions per patient. A significant decrease of manifestations during 4 years of follow-up (mean clinical lesions 0.5, p = 4. Predictors associated with a severe disease course include the site of inflammation (pelvis, lower extremity, clavicle), increased erythrocyte sedimentation rate, and multifocal disease at first documentation. The previously published composite PedCNO disease activity score was analyzed revealing a PedCNO70 in 55% of the patients at 4YFU. Conclusion An improvement of physician global disease activity (PGDA), patient reported overall well-being and imaging-defined disease activity measures was documented, suggesting that inactivity of CNO disease can be reached. PedCNO score and especially PGDA, MRI-defined lesions and in a number of patients also the C-HAQ seem to be reliable parameters for describing disease activity. The identification of risk factors at the beginning of the disease might influence treatment decision in the future.

Abstract Background Limping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician. Case presentation We describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease. Conclusions although trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture.

Background and Objectives: The diagnosis of rheumatic diseases in children is challenging and requires the use of advanced imaging examinations such as whole-body magnetic resonance imaging (MRI). Whole-body MRI allows visualization of bone marrow edema (BME), muscle edema, joint effusion and changes in the soft tissues surrounding the joints. The aim of this study was to collect and compare whole-body MRI findings, laboratory results and clinical manifestations of pediatric patients with suspected rheumatic disease. Materials and methods: In this retrospective single-center study, 33 patients who underwent whole-body MRI were included. Their age ranged from 9 to 17 years, and 24 (72.73%) of the patients were female. Patients were diagnosed as follows: juvenile idiopathic arthritis (27.27%), juvenile idiopathic inflammatory myopathies (21.21%), chronic nonbacterial osteomyelitis (21.21%) and other medical conditions (30.30%), such as arthritis associated with infection, scleroderma, Takayasu arteritis, polyarteritis nodosa and joint damage. Results: The most common symptom reported by 26 (79.79%) patients was pain. On physical examination, the limitation of joint mobility was examined in 17 (51.51%), swelling of the joints was observed in 12 (36.36%) patients and decreased muscle strength was noticed in 11 (33.33%) patients. An increase in the C-reactive protein (12%), erythrocyte sedimentation rate (9%), leukocyte count (9%) and creatine kinase (CK) (18%) was observed. Whole-body MRI revealed myositis (30%), joint effusion (27%) and BME (24%). The statistical analysis showed a significant relationship between myositis and the elevated CK level (p < 0.05). Conclusions: The most common symptom in the studied population was pain, while the limitation of joint mobility was found in more than half of patients. Myositis was the most commonly imaged lesion on the whole-body MRI and it was related to an increase in the CK level.

Abstract Background Chronic 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. Methods A 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. Results 36 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. Conclusions Following 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.

Abstract 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.

Abstract Objectives 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. Conclusion Carriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases.

Background: Limping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician. Case presentation: We describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease. Conclusions: although trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture. [ABSTRACT FROM AUTHOR]

Objective. 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. Methods. 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. Results. 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. Conclusion. The CNO CDAS was developed and validated for disease monitoring and assessment of treatment effectiveness. CHOIR provided a comprehensive framework for future CER. [ABSTRACT FROM AUTHOR]

Background/aim: 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. Materials and methods: 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. Results: 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. Conclusion: In this multicenter study, CNO with vertebral and mandibular involvement and high ESR at diagnosis were associated with recurrence. [ABSTRACT FROM AUTHOR]

Abstract Background Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118–1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3–19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228–1237, 2014). Case presentation A 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease. Conclusions Children and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation.

Differential diagnosis of bacterial osteomyelitis (BOM) and chronic nonbacterial osteomyelitis (CNO) is challenging. Pediatric CNO can be diagnosed at around 10 years of age and when CNO cases involve only the jaw, it is difficult to make a diagnosis in a young child. A 3-year-old female developed CNO at the jaw alone. She presented with no fever, right jaw pain, mild trismus, and a preauricular facial swelling around the right mandible. Computed tomography (CT) revealed a hyperostotic right mandible, with osteolytic and sclerotic changes associated with periosteal reaction. At first, we suspected BOM and antibiotics were administered. Subsequently, CNO was diagnosed, and the patient received flurbiprofen (a nonsteroidal anti-inflammatory drug (NSAIDs)). Lack of a sufficient response led to successful treatment with a combination of oral alendronate and flurbiprofen. Physicians should be aware of CNO, a rare autoinflammatory noninfectious bone disease of unknown etiology, even in young children, although the disease mostly affects older children and adolescents.

Background: Chronic 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. Methods: A 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. Results: 36 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. Conclusions: Following 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: 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. Conclusion: Carriage of HLA-B*27 is associated with greater risk of developing CNO, particularly in male cases. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118–1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3–19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228–1237, 2014). Case presentation: A 13-year-old Caucasian boy presented with 1 month of progressive lower-extremity pain, weakness, and weight loss. His physical examination was notable for cachexia, lower-extremity weakness, and chorea. Labs revealed normocytic anemia and systemic inflammation. Imaging revealed symmetric abnormal marrow signal in the pelvis and upper femurs. Pathologic examination of the bone revealed chronic inflammation consistent with chronic nonbacterial osteitis. Endoscopy revealed colonic inflammation consistent with inflammatory bowel disease. Conclusions: Children and adolescents with musculoskeletal pain lasting more than 2 weeks with systemic signs or symptoms like weight loss should prompt evaluation for systemic inflammatory disorders such as chronic nonbacterial osteitis, which can occur in isolation or associated with inflammatory bowel disease. This patient also had a nonspecific neurologic abnormality, chorea, which resolved with treatment of underlying inflammatory disorder. These extraintestinal manifestations may be concurrent with or precede intestinal inflammation, requiring a high index of suspicion when investigating nonspecific systemic inflammation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical and radiological findings of the patients with chronic recurrent multifocal osteomyelitis (CRMO) and to present the benefits of using whole-body magnetic resonance imaging (WBMRI) in these patients and the changes we have made in the technique. Methods: A total of 45 patients who underwent WBMRI between 2017 and 2021 were included in the study. All WBMRI scans included coronal short tau inversion recovery (STIR), coronal T1W, and sagittal spinal STIR sequences. The examination time was 40 min on average. All WBMRIs were evaluated at two different time. At first assessment, only coronal STIR images were evaluated in all patients. In the second assessment, the same patients evaluated with all the sequences. The contribution of coronal T1W and sagittal STIR sequences to the diagnosis was investigated by comparing the first evaluation with the second evaluation. Thirty five patients were diagnosed with CRMO. The remaining 10 patients had other inflammatory, infective, and neoplastic diseases. The diagnosis of 15 patients with CRMO was based on bone marrow biopsy results. Also, biopsy was performed in 10 patients diagnosed as non-CRMO. Results: Most of the patients had multifocal bone lesions, particularly in the metaphyses adjacent to the epiphyseal region. The bones of the lower extremities were the most commonly affected. The mean delay in diagnosis was 17 months (0-96), and the follow-up period was 20 months (1-47) in a total of 35 patients, with a recurrence rate of 28%. In most patients (88%), lesions could be identified from coronal STIR images alone at the initial evaluation. However, in 5 patients whose diagnosis was missed when evaluated only from coronal STIR images, lesion identification and possible preliminary diagnosis were detected only with coronal T1W and sagittal STIR images in the second look. Conclusion: WBMRI is an important examination of systemic diseases such as CRMO that involve multiple sites. In addition to coronal STIR sequences, coronal T1-weighted and sagittal STIR sequences are important in identifying other infective-inflammatory diseases and particularly hematological malignant processes in the differential diagnosis of CRMO. [ABSTRACT FROM AUTHOR]

Differential diagnosis of bacterial osteomyelitis (BOM) and chronic nonbacterial osteomyelitis (CNO) is challenging. Pediatric CNO can be diagnosed at around 10 years of age and when CNO cases involve only the jaw, it is difficult to make a diagnosis in a young child. A 3-year-old female developed CNO at the jaw alone. She presented with no fever, right jaw pain, mild trismus, and a preauricular facial swelling around the right mandible. Computed tomography (CT) revealed a hyperostotic right mandible, with osteolytic and sclerotic changes associated with periosteal reaction. At first, we suspected BOM and antibiotics were administered. Subsequently, CNO was diagnosed, and the patient received flurbiprofen (a nonsteroidal anti-inflammatory drug (NSAIDs)). Lack of a sufficient response led to successful treatment with a combination of oral alendronate and flurbiprofen. Physicians should be aware of CNO, a rare autoinflammatory noninfectious bone disease of unknown etiology, even in young children, although the disease mostly affects older children and adolescents. [ABSTRACT FROM AUTHOR]

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. Methods: We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Results: Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn's disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. Conclusions: The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment. [ABSTRACT FROM AUTHOR]

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.

BackgroundChronic nonbacterial osteomyelitis (CNO) is an auto-inflammatory bone disease that usually develops in childhood. Spinal involvement is a common manifestation of CNO, but it is rare for CNO to lead to rapid progression of scoliosis deformity. Here we present a 9-year-old girl with acute scoliosis with CNO and scoliosis progressed rapidly in 2 months.Case PresentationA 9-year-old girl presented bilateral shoulder inequality with pain in the left hypochondrium for 2 months. Standing spinal x-rays showed right convex scoliosis with a 25° Cobb angle. Chest magnetic resonance imaging (MRI) showed that the T8 vertebra was flattened and local bone was destroyed with bone marrow edema. The bone biopsy showed evidence of fibrosis and chronic inflammatory changes with no specific diagnosis. One month later, her scoliosis and bone destruction deteriorated obviously. Thoracic vertebra MRI showed that the T8 vertebra had a compression fracture. 99mTc-MDP whole-body bone scintigraphy showed intense uptake at T8/9 and the right sacroiliac joint. She was diagnosed with CNO accompanied by rapidly progressive scoliosis. The scoliosis was successfully treated with adalimumab and zoledronic acid, which showed significant improvement after 6 months of follow-up.ConclusionZoledronic acid and adalimumab successfully treated CNO with rapidly progressive scoliosis, but could not prevent vertebral compression.

Chronic nonbacterial osteomyelitis (CNBO) is an autoinflammatory bone disease with a low incidence in association with juvenile idiopathic arthritis (JIA). The autoimmune mechanisms are suspected in the pathogenesis of the disease, and whenever it complicates JIA, it changes the initial arthritis therapeutic approach. The authors present the case of a boy with JIA, enthesitis-related arthritis (ERA) subtype, complicated with recurrent right clavicle CNBO, along with the clinical evolution and the treatment strategies. [ABSTRACT FROM AUTHOR]

Abstract Objective The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). Methods Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. Results Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7–13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0–72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1–7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. Conclusions The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications.

Abstract Objective To assess the first-year features of patients with chronic nonbacterial osteomyelitis (CNO). Methods Patients with a diagnosis of CNO, disease duration of under 13 months, and first registration in the German National Pediatric Rheumatologic Database (NPRD) between 2009 and 2018 were included in this cross-sectional analysis. Results Of 774 documented patients, 62.8% were female, and all patients had a median age of 11 years. The most affected clinical sites were the tibia (29.7%), pelvis (28.0%), and femur (27.8%). HLA-B27 was positive in 48 of 314 analyzed patients (15.3%). In 406 patients, an X-ray was performed at the first visit; X-ray results showed osteosclerosis/−lysis in 34.0% and hyperostosis in 14.5% of the patients. MRI scans (focal and whole-body scans) were performed in 648 patients, and 81.5% showed a positive TIRM/STIR signal. A total of 84.7% of the patients were administered nonsteroidal anti-inflammatory drugs, 9.6% were administered oral glucocorticoids, 10.8% were administered disease-modifying anti-rheumatic drugs (DMARDs), and 6.1% were administered bisphosphonates. An evaluation of the patient’s questionnaire showed an overall well-being (NRS 0–10) of 2.0. The PedCNO disease “activity” score revealed a 70% improvement in variables in 43% of patients in the initial 1-year follow-up. Copresentation with diagnostic criteria of pediatric enthesitis-related arthritis was rare. Conclusion To our knowledge, the NPRD cohort seemed to be the largest cohort of children and adolescents suffering from CNO worldwide. Most patients were treated effectively with NSAIDs, and only a small group of patients was administered additional medication. The patient-defined measures of disease activity had a moderate impact on patients’ daily lives. Trial registration Not applicable.

Objective: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disease that is gaining recognition from clinicians and researchers. We aim to publish data from our cohort of patients with CNO living in the northwestern United States to increase the awareness of specific demographics, characteristics, and presentation of this rare disease.Methods: A retrospective chart review was performed of our electronic medical records. Patients with complete chart records who met criteria for a diagnosis of CNO from 2005 to 2019 were included. Extracted data including patient demographics, bone biopsy results, and lesion locations on advanced imaging were analyzed. King County census data were used to calculate the annual new case rate within our center.Results: A total of 215 CNO cases were diagnosed at our large tertiary pediatric hospital. The majority of cases were of White race residing in Washington's most populous county, King County. Most cases were diagnosed in 2016 to 2019, showing a significant increase in the annual case rate from 8 to 23 per million children in King County, though there did not appear to be a seasonal predilection. Biopsy rate decreased from 75% to 52%. One hundred fifty-two (71%) children had family history of autoimmunity. With increasing use of whole-body magnetic resonance imaging (WB-MRI), results showed 68% had multiple lesions.Conclusion: CNO has been diagnosed at an increased rate in recent years. WB-MRI may assist in identifying other lesions that may be asymptomatic on presentation. Bone biopsy is still required in some children at the time of diagnosis. [ABSTRACT FROM AUTHOR]

Background: Chronic nonbacterial osteomyelitis (CNO) is a pediatric autoinflammatory disorder presenting with sterile inflammatory bone lesions. Whole-body MRI (WBMRI) has most recently emerged for disease assessment, but data are limited. Purpose: The purpose is to evaluate the imaging findings and patterns of CNO on WBMRI in a series of Greek pediatric patients. Material and Methods: Whole-body magnetic resonance imaging studies of all children with documented CNO, performed in a single tertiary center, were retrospectively reviewed. WBMRI included coronal T1 and short-tau inversion recovery (STIR), whole spine sagittal STIR, and ankle/foot sagittal STIR images. High signal intensity lesions on STIR images corresponding to bone marrow edema were recorded. The SPSS v.20 statistical package was used for descriptive statistics. Results: Twenty children were included (mean age: 12, range: 6–16 years) with 1–31 lesions (mean: 11.8) on WBMRI. Two children had unifocal disease localized at the clavicle, three paucifocal (1–4 lesions), and 15 multifocal bone involvement. All but two children presented with ankle pain and exhibited lesions at the bones of the ankle joint (90%) followed by the knee (50%) and pelvis (10%). The tibia was the most frequently affected bone (70%) followed by calcaneus (60%), fibula (50%), femur (45%), talus, and metatarsals (45%). No lesions in the cervical, thoracic, lumbar spine, and mandible were documented. Only small sacral lesions were seen in 25% of patients with the extensive peripheral disease. Bilateral metaphyseal and epiphyseal involvement with transphyseal extension were common, but the periosteal reaction and well-defined lesion margins were rare. Conclusion: Frequent involvement of the foot and ankle and paucity of substantial spinal involvement were seen in Greek pediatric patients with CNO. [ABSTRACT FROM AUTHOR]

Abstract Background Based on the recently developed ChRonic nonbacterial Osteomyelitis MRI Scoring tool (CROMRIS), we developed a radiological activity index (RAI-CROMRIS) to obtain a quantification of the overall bone involvement in individual patients. Methods Whole Body Magnetic Resonance Imaging (WB-MRI) images were scored according to parameters included in the RAI-CROMRIS: bone marrow hyperintensity, signal extension, soft tissue/periosteal hyperintensity, bony expansion, vertebral collapse. These parameters were evaluated for each bone unit yielding a score from 0 to 7 and summed up as RAI-CROMRIS including all bone units. We assessed clinical disease activity using a physician global assessment (PGA) and radiological findings in 76 treatment-naïve patients; 46 of 76 were evaluated at 6 and 12 months after initial WB-MRI. Quantitative variables were compared using the Mann-Whitney U test for unmatched groups and the Wilcoxon signed-rank test for paired groups. Correlation was evaluated using Spearman’s rank coefficient (rs). Results There was a significant correlation between RAI-CROMRIS and PGA (r s = 0.32; p = 0.0055), between RAI-CROMRIS and presence of elevated erythrocyte sedimentation rate (p = 0.013) and C-reactive protein (p = 0.0001) at baseline. The RAI-CROMRIS decreased from a median of 17 at baseline to 12 at 6 months (p = 0.004) and remained stable (median 11) at 12 months. A correlation between the RAI-CROMRIS and the PGA was observed at baseline (r s = 0.41; p = 0.004) and during follow up at 6 months (r s = 0.33; p = 0.025) and 12 months (r s = 0.38; p = 0.010). The baseline RAI-CROMRIS (median 20) was significantly higher in patients who subsequently received bisphosphonates than in patients who received other treatments (median 12) and decreased significantly after bisphosphonates (p = 0.008). Conclusions The RAI-CROMRIS was correlated with clinical and laboratory measures of disease activity showing significant short-term changes following treatment with bisphosphonates. This tool could be used in clinical practice and clinical trials after validation.

Abstract Background Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a condition characterized by sterile bone inflammation, usually occurring in childhood. Although the etiology remains unclear, this condition has been associated with inflammatory bowel disease (IBD). Primary sclerosing cholangitis (PSC) and Autoimmune Hepatitis (AIH) are also uncommon pediatric conditions with a known association with IBD. Case presentation We present a unique case of a pediatric patient with an initial diagnosis of CRMO, with subsequent diagnosis of autoimmune hepatitis and PSC overlap, and eventually IBD. Conclusions Patients with CRMO may also develop PSC in addition to IBD, further highlighting the importance of IBD pathophysiology in both conditions. Clinical screening of associated gastrointestinal findings may be of value in patients with CRMO.

Abstract Background Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory disease affecting bone with considerable phenotypic heterogeneity and variable association with other autoinflammatory conditions. Disease pathogenesis is incompletely understood, and treatment protocols vary between physicians with no clinical treatment guidelines available prior to 2017. Although CNO was previously considered benign, it is now clear that long-term sequelae do occur. The aim of this study is to provide a detailed phenotypic description of children and adolescents with CNO who attended tertiary paediatric rheumatology services in Ireland between September 2017 and September 2019, their disease course, treatment and outcomes. Methods This study involved retrospective review of clinical notes, laboratory, radiology and histology results of Irish children and adolescents with CNO who are currently attending tertiary paediatric rheumatology services. The Bristol diagnostic criteria were applied retrospectively; only patients who met these criteria were included. Criteria for remission and partial response were based on the Childhood Arthritis and Rheumatology Research Alliance (CARRA) criteria for treatment failure. Results Forty-four children and adolescents were recruited. Demographics in terms of age of onset, gender and number of sites were similar to those previously reported. Overall, 18/44 (40.9%) had extraosseous manifestations associated with CNO; 12/44 (27.2%) had cutaneous involvement. All patients received a regular nonsteroidal anti-inflammatory drug (NSAID) after diagnosis with 27/44 (61.4%) requiring at least 1 second-line medication. Second-line agents used in this cohort were bisphosphonates, methotrexate and TNF-blockers. No patients received systemic corticosteroids. Conclusion This national cohort showed a high prevalence of extraosseous involvement and a low response rate to NSAID treatment. This may reflect a more inflammatory phenotype and highlights the need to define different subtypes of CNO.

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. Methods: We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Results: Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn’s disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. Conclusions: The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment.

Purpose of Review: To explain the central role of magnetic resonance imaging (MRI) in the diagnosis and follow-up of chronic nonbacterial osteomyelitis (CNO) in children and adolescents, centering on practical technical aspects and salient diagnostic features. Recent Findings: In the absence of conclusive clinical features and widely accepted laboratory tests, including validated disease biomarkers, MRI (whether targeted or covering the entire body) currently plays an indispensable role in the diagnosis and therapy response assessment of CNO. Whole-body MRI, which is the reference imaging standard for CNO, can be limited to a short tau inversion recovery (STIR) coronal image set covering the entire body and a STIR sagittal set covering the spine, an approximately 30-min examination with no need for intravenous contrast or diffusion-weighted imaging. The hallmark of CNO is periphyseal (metaphyseal and/or epi-/apophyseal) osteitis, identified as bright foci on STIR, with or without inflammation of the adjacent periosteum and surrounding soft tissue. Response to bisphosphonate treatment for CNO has some unique MRI findings that should not be mistaken for residual or relapsing disease. Summary: Diagnostic features and treatment response characteristics of MRI in pediatric CNO are discussed, also describing the techniques used, pitfalls encountered, and differential diagnostic possibilities considered during daily practice. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate demographic, clinical, laboratory, imaging, histopathology characteristics, and treatment responses of children with Chronic nonbacterial osteomyelitis (CNO). Methods: Retrospective multi-center case series study of pediatric patients diagnosed with CNO treated at five tertiary centers in south China. Results: Totally there were 18 patients diagnosed as CNO between 2014 and 2020. The median age of onset was 9.2 years (range 3.7–13.1) and 55.6% were female. Median delay in diagnosis was 10.9 months (range 1.0–72.0). The most frequent presenting symptoms were bone pain (100%) and fever (44.4%). Most patients had more than one lesion (median of 5, range 1–7). Most frequently affected bones were tibiofibula (88.9%) and femur (77.8%). The MRI characteristics mainly presented as bone edema and hyperintensity in bone marrow. Bone biopsy was conducted in 11 patients (61.1%) with inflammatory cells infiltration manifested as chronic osteomyelitis, and none showed bacterial infection or tumor. In treatment, non-steroid anti-inflamatory drugs (NSAIDs) is used as the first-line drug followed by steriods, methotexate (MTX), salazosulfadimidine (SASP), Bisphosphonates and TNF-α inhibitor. Two refractory cases received combination therapy with Bisphosphonates and TNF-α inhibitor, and achieved good therapeutic effect. Conclusions: The present study described a multicenter series of CNO from south China and highlighted the clinical features, laboratory tests, imaging characteristics and treatment outcomes. Increasing awareness of this disease is important to decrease time to diagnosis, improve access to treatment, and reduce complications. [ABSTRACT FROM AUTHOR]

Abstract Background Studies evaluating treatment responses for chronic nonbacterial osteomyelitis (CNO) are lacking. We aimed to measure and compare response rates of medical treatments, time to response of medical treatments among patients with CNO of the mandible, and describe bacterial contamination rates from biopsy. Methods We conducted a retrospective chart review of all patients diagnosed with CNO of mandible between 2003 and 2017 and extracted demographic, clinical, laboratory, imaging and surgical data. Detailed medication use and response to medications were recorded. The primary outcome was response to medical treatments defined as improvement of presenting symptoms, inflammatory markers, and imaging if available. Medical treatments included nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti rheumatic drugs (DMARDs), anti-tumor necrosis factor (TNF) therapy, and pamidronate. Descriptive analysis was performed when appropriate. Multivariable logistic regression and Kaplan-Meier curves were applied to compare the responses to medical treatments and time to full response. Results We identified 22 patients with a median age of 11 and 36% were female. Four patients (18%) had multifocal bone lesions. CT findings (n = 21) showed lytic lesions (62%) and sclerosis (90%). MRI (n = 14) revealed hyperintensity within bone marrow (100%), soft tissue (71%) and bony expansion (71%). Non-antibiotic treatments including NSAIDs (n = 18), glucocorticoids (n = 10), DMARDs (n = 9), anti-TNF therapy (n = 5) and pamidronate (n = 6) were applied. Rates of full responses to anti-TNF therapy (60%) and pamidronate (67%) were higher than that to NSAIDs (11%) (p

Chronic nonbacterial osteomyelitis (CNO) is an uncommon autoinflammatory disorder. Significant effort has recently been spent to better define and treat this disorder including development of consensus treatment protocols, validate disease activity tools, and refining classification criteria. However, the underlying immunopathogenesis of the disease remains elusive. In this report, we describe the simultaneous onset of CNO in siblings. A pathogenic gene mutation was not identified, and these sisters lacked a similar biomarker profile. This report highlights that if a genetic predisposition for CNO exists, it may be related to complex polygenic or multifactorial mechanisms of disease evolution., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Primary chronic osteomyelitis (PCO) of the jaw is a non-infectious, inflammatory state of the jawbone of unknown etiology. In recurrent periods, these patients often exhibit swelling of the cheek, impaired ability to open their mouth as well as pain. Available treatments today include anti-inflammatory or antiresorptive drugs, hyperbaric oxygen, surgical decortication or resection followed by reconstruction where none of them have been described to lead to restored anatomy and complete relief of symptoms. We here report the unexpected complete regression of all clinical symptoms of PCO within three months after initiating pubertal suppression therapy with a gonadotropin-releasing hormone analogue in a 9-year-old girl with PCO of the jaw and early onset of pubertal development. Radiology of the jawbone confirmed complete PCO remission when performed 18 months after starting the hormone suppression therapy. To our knowledge, total regression of PCO in such a short period of time has not been described earlier suggesting an effect of the anti-hormonal therapy per se. In this case report, we discuss possible underlying mechanisms and hypothesize that anti-hormonal treatment could be a potential effective treatment in patients with PCO of the jaw.

Background: Based on the recently developed ChRonic nonbacterial Osteomyelitis MRI Scoring tool (CROMRIS), we developed a radiological activity index (RAI-CROMRIS) to obtain a quantification of the overall bone involvement in individual patients. Methods: Whole Body Magnetic Resonance Imaging (WB-MRI) images were scored according to parameters included in the RAI-CROMRIS: bone marrow hyperintensity, signal extension, soft tissue/periosteal hyperintensity, bony expansion, vertebral collapse. These parameters were evaluated for each bone unit yielding a score from 0 to 7 and summed up as RAI-CROMRIS including all bone units. We assessed clinical disease activity using a physician global assessment (PGA) and radiological findings in 76 treatment-naïve patients; 46 of 76 were evaluated at 6 and 12 months after initial WB-MRI. Quantitative variables were compared using the Mann-Whitney U test for unmatched groups and the Wilcoxon signed-rank test for paired groups. Correlation was evaluated using Spearman's rank coefficient (rs). Results: There was a significant correlation between RAI-CROMRIS and PGA (rs = 0.32; p = 0.0055), between RAI-CROMRIS and presence of elevated erythrocyte sedimentation rate (p = 0.013) and C-reactive protein (p = 0.0001) at baseline. The RAI-CROMRIS decreased from a median of 17 at baseline to 12 at 6 months (p = 0.004) and remained stable (median 11) at 12 months. A correlation between the RAI-CROMRIS and the PGA was observed at baseline (rs = 0.41; p = 0.004) and during follow up at 6 months (rs = 0.33; p = 0.025) and 12 months (rs = 0.38; p = 0.010). The baseline RAI-CROMRIS (median 20) was significantly higher in patients who subsequently received bisphosphonates than in patients who received other treatments (median 12) and decreased significantly after bisphosphonates (p = 0.008). Conclusions: The RAI-CROMRIS was correlated with clinical and laboratory measures of disease activity showing significant short-term changes following treatment with bisphosphonates. This tool could be used in clinical practice and clinical trials after validation. [ABSTRACT FROM AUTHOR]