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Background: Chronic nonbacterial osteomyelitis (CNO) is a rare non-infectious inflammatory musculoskeletal disease where imaging plays a key diagnostic role. Vertebral and mandibular lesions are frequent manifestations, meaning their awareness is crucial for the neuroradiologist to avoid delays in diagnosis and treatment. Objective: Characterize vertebral and mandibular CNO lesions on imaging to assist practicing neuroradiologists in better identifying this disease. Materials and methods: Retrospective review of all CNO patients of our pediatric center, including only patients with vertebral or mandibular lesions. All imaging exams were analyzed to record lesion characteristics. Results: We included 13 patients (six male). The mean age of onset was 12.3 years. Ten patients had only vertebral lesions, two had only mandibular lesions, and one had both. For patients with vertebral lesions, the median number of levels affected was three, 81.8% had multiple levels affected, 90.0% had dorsal spine lesions, 72.7% had platyspondyly, and 81.8% had inflammatory changes. All vertebral lesions had at least partial resolution of inflammatory findings, the mean time of lesion activity was 2.5 years, and recurrence occurred in 27.3%. Three patients had sacral lesions, all with sacroiliitis. In patients with mandibular lesions, all had unilateral lesions involving the mandibular ramus, all had hyperostosis, periosteal reaction, bone edema, and soft tissue inflammation, all had partial resolution on follow-up, and one had recurrence. Conclusion: CNO vertebral lesions are not rare, are often multiple, predominantly affect dorsal levels, and most result in vertebral height loss. Resolution of vertebral inflammatory lesions is frequent, but so is recurrence. Sacral lesions may be present and result in sacroiliitis. The mandible may be a site of unifocal disease, typically affecting the ramus, with prominent bony changes and soft tissue inflammation. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, non-infectious inflammatory disease with a prevalence of 1 to 2/106, causing multiple lytic bone lesions. There are no established protocols for treating CRMO; thus, current practice is largely empirical. Data on the use of zoledronic acid (ZA) in juvenile CRMO are scarce. A 12-year-old male child with a history of multiple aseptic osteomylitis, affecting the chest wall, right ankle, and wrist, had no fever. Cultures and a bone biopsy ruled out infection or malignancy. The patient's condition stayed stable while taking naproxen (20 mg/kg/day) and methotrexate (10 mg/week) for 1.5 years until he experienced right elbow pain, swelling, no overlying skin erythema, and a restricted range of motion. The laboratory tests all came back normal, including white blood cell (WBC) count, erythrocyte sedimentation rate, C-reactive protein, and immunoglobin assays. The magnetic resonance imaging showed a focal lesion in the medial humeral condyle with increased signal intensity on T2 and short tau inversion recovery, mild joint effusion, and no cortical break. Thus, intravenous ZA infusion commenced at 0.0125 mg/kg initially, followed by 0.025 mg/kg 3 months later, with a marked improvement in the patient's clinical symptoms and radiological findings. Non-steroidal anti-inflammatory drugs and methotrexate were initially effective in treating our patient's condition, but a recurrence necessitated treatment modification. To the best of our knowledge, this case is the first documented instance of the use of ZA in CRMO in Iraq and Arab nations. [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]

Chronic recurrent multifocal osteomyelitis (CRMO), an autoinflammatory bone disorder characterized by non-bacterial osteomyelitis causing recurrent multifocal bone lesions, is a well-known, yet uncommon pediatric condition that rarely affects adults; to date, it has never been diagnosed over the age of 75. The following report will discuss the first octogenarian diagnosed with CRMO and therefore represents an exceptionally rare presentation of a rare disease. An 83-year-old woman presented with progressive right shoulder, forearm, and hip pain, with associated weight loss and global weakness, requiring a wheelchair for mobility. Imaging revealed a pathologic right ulna fracture in addition to lytic lesions of the right proximal humerus and proximal femur. The clinical picture was thus that of a patient with probable multiple myeloma versus metastatic disease. After an extensive workup, however, the lesions were not malignant; histologic findings were instead suggestive of chronic osteomyelitis with negative cultures. Given the multifocal nature of this condition, combined with a lack of clinical symptoms of infection, a diagnosis of CRMO was rendered. The patient underwent intramedullary nailing of the right femur and splinting of the ulna, with a subsequent remarkable recovery to painless ambulation, complete union of the right ulna fracture, and resolution of the lytic lesions without receiving any targeted medical treatment. This case highlights the importance of maintaining CRMO on the differential for multifocal skeletal lesions, regardless of age. Performing a thorough workup with necessary imaging, biopsy, and culture are critical to establishing this diagnosis, which can only made as a diagnosis of exclusion. [ABSTRACT FROM AUTHOR]

This article discusses a case of chronic nonbacterial osteomyelitis (CNO) complicated by recurrent erythema nodosum (EN) and its successful treatment with salazosulfapyridine (SASP). CNO is a condition characterized by bone lesions and can also present with mucocutaneous symptoms. EN is a skin condition associated with inflammation of the subcutaneous tissue. The patient initially received naproxen for treatment but experienced persistent symptoms. SASP was then introduced and led to remission of both CNO and EN. The use of SASP as a second-line treatment for refractory CNO and EN is suggested. [Extracted from the article]

The paediatric metaphysis is afflicted by a wide range of pathological processes as it is the most metabolically active and well-vascularised part of the developing skeleton. This review focuses on metaphyseal marrow signal change detected with magnetic resonance imaging, which is most often occult on radiographs. When bilateral, these imaging appearances frequently present a diagnostic quandary. This review assists the radiologist to confidently dismiss physiological signal change and confidently work through the differential diagnosis. This is achieved by illustrating a practical method of classifying signal change into four categories: physiological red marrow, red marrow reconversion, marrow infiltration, and oedema-like marrow signal intensity. In doing so, various pathological entities are reviewed along with imaging pearls and next-step investigations. [ABSTRACT FROM AUTHOR]

Background: Chronic recurrent multifocal osteomyelitis is a rare autoimmune disorder causing inflammatory joint lesions. It has an estimated prevalence of 1-2 per million while adult-onset disease constitutes only 6.3% of patients. Case report: We present a case of a 44 years old male who presented to the rheumatology clinic with lower back pain for twelve years. Magnetic resonance imaging of the lumbosacral spine showed ovoid areas of abnormal signal intensities along superior and inferior endplates of multiple vertebrae of the dorsolumbar and sacral spine. Computed tomography guided biopsy of L4 vertebrae was done. Histopathology revealed linear cores of degenerating fibrocartilage focally exhibiting small spicules of mineralized bone and fibro-collagenous tissue. He initially did not respond to traditional therapy. His symptoms improved with the addition of a Janus Kinase inhibitor. To the best of our knowledge, this is the first case of chronic recurrent multifocal osteomyelitis to be reported from Pakistan. [ABSTRACT FROM AUTHOR]

(1) Background: Whole-body magnetic resonance imaging (WB-MRI) is central to defining total inflammatory burden in juveniles with arthritis. Our aim was to determine and compare the initial distribution of lesions in the WB-MRI in patients with chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), their overlapping syndrome (OS), and with Non-specific Arthropathy (NA). (2) Methods: This retrospective single center study was performed on an Avanto 1.5-T MRI scanner with a dedicated multichannel surface coil system. A total of 173 pediatric patients were included with the following final diagnoses: CRMO (15.0%), JIA (29.5%), OS (4.6%), and NA (50.9%). (3) Results: Bone marrow edema (BME) was the most common abnormality, being seen in 100% patients with CRMO, 88% with OS, 55% with JIA, and 11% with NA. The bones of the lower extremities were the most affected in all compared entities. Effusion was seen in 62.5% children with OS, and in 52.9% with JIA, and in CRMO and NA, the exudate was sporadic. Enthesitis was found in 7.8% of patients with JIA and 3.8% with CRMO, and myositis was seen in 12.5% of patients with OS and in 3.9% with JIA. (4) Conclusions: The most frequent indication for WB-MRI in our center was JIA. The most common pathology in all rheumatic entities was BME, followed by effusion mainly seen in in OS and JIA. Enthesitis and myositis were less common; no case was observed in NA. [ABSTRACT FROM AUTHOR]

Objective: Chronic recurrent multifocal osteomyelitis (CRMO) is the most common autoinflammatory disease of the bone characterized by pain and inflammatory lesions without an infectious agent. The aim of this study is to evaluate the clinical, laboratory, and imaging features and treatments of paediatric patients with CRMO followed in our pediatric rheumatology clinic. Material and Methods: Medical records of ten patients diagnosed with CRMO according to Bristol diagnostic criteria between January 2018 and June 2021 were retrospectively reviewed. Results: The mean age at diagnosis was 9.3 years, and eight of the patients were male. One patient had concomitant psoriasis, two patients had familial Mediterranean fever and one patient had a history of immunoglobulin A vasculitis. Half of the patients had a moderate acute phase reactant elevation. The most frequently involved bones were the lower extremity bones. While localized magnetic resonance imaging (MRI) was the most commonly used imaging modality in the diagnosis of CRMO, silent bone lesions (15%) were detected only by the whole-body MRI. Non-steroidal anti-inflammatory drug (NSAID) was given to all patients. As second-line therapy, methotrexate and pamidronate were employed on seven and five patients respectively. Three of the patients received anti-TNF treatment (etanercept and infliximab) as the third-line therapy. Imaging with whole-body MRI is important due to clinically silent bone lesions, especially in the course of CRMO. Conclusion: Concomitant familial Mediterranean fever was not rare in cases with CRMO and treatment of CRMO might be challenging due to the need for anti-TNF treatment in a considerable number of patients. [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 Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by chronic vasculitis involving small to medium sized arteries, granulomatous inflammation of the upper and lower respiratory tracts, pauci-immune necrotizing glomerulonephritis, as well as vasculitis of other organs. Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory syndrome characterized by sterile bone inflammation. Case presentation We report a case of CRMO that was doing well on non-steroidal anti-inflammatory drugs (NSAID for 6 years and then developed ANCA positive limited GPA presenting with pyoderma gangrenosum, persistent bilateral otalgia with serous otitis, otorrhea, then sensorineural hearing loss. Conclusion This is the first report of limited GPA initially presenting as pyoderma gangrenosum in a patient with underlying CRMO. It is unclear how the pathology of an autoimmune and an autoinflammatory condition can overlap.

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]

Background: 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. Objective: To characterize the MR imaging features and patterns of pediatric spinal CRMO/CNO. Materials and methods: 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. Results: Forty-two patients were included (F:M, 30:12); median age was 10 years (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%). Conclusion: 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. [ABSTRACT FROM AUTHOR]

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease that most commonly affects children and adolescents causing significant pain and damage to bones. The absence of diagnostic criteria and biomarkers, an incomplete understanding of the molecular pathophysiology, and lack of evidence from randomized and controlled trials make the diagnosis and care challenging. This review provides an overview of the clinical and epidemiological features of CNO and displays diagnostic challenges and how they can be addressed following strategies used internationally and by the authors. It summarizes the molecular pathophysiology, including pathological activation of the NLRP3 inflammasome and IL-1 secretion, and how these observations can inform future treatment strategies. Finally, it provides a summary of ongoing initiatives aiming at classification criteria (ACR/EULAR) and outcome measures (OMERACT) that will enable the generation of evidence through clinical trials. Scientific efforts have linked molecular mechanisms to cytokine dysregulation in CNO, thereby delivering arguments for cytokine blocking strategies. Recent and ongoing collaborative international efforts are providing the basis to move toward clinical trials and target directed treatments for CNO that find approval by regulatory agencies. [ABSTRACT FROM AUTHOR]

Background: Granulomatosis with polyangiitis (GPA) is an autoimmune disease characterized by chronic vasculitis involving small to medium sized arteries, granulomatous inflammation of the upper and lower respiratory tracts, pauci-immune necrotizing glomerulonephritis, as well as vasculitis of other organs. Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory syndrome characterized by sterile bone inflammation. Case presentation: We report a case of CRMO that was doing well on non-steroidal anti-inflammatory drugs (NSAID for 6 years and then developed ANCA positive limited GPA presenting with pyoderma gangrenosum, persistent bilateral otalgia with serous otitis, otorrhea, then sensorineural hearing loss. Conclusion: This is the first report of limited GPA initially presenting as pyoderma gangrenosum in a patient with underlying CRMO. It is unclear how the pathology of an autoimmune and an autoinflammatory condition can overlap. [ABSTRACT FROM AUTHOR]

Abstract Introduction Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory bone disorder with predominantly paediatric onset. Children present with multifocal osteolytic lesions accompanied by bone pain and soft tissue swelling. Patients often exhibit extraosseous co-morbidities such as psoriasis, inflammatory bowel disease, and arthritis. Objectives Comparison of children with two different phenotypes of CRMO defined by presence or absence of extraosseous co-morbidities. Methods Children diagnosed with CRMO at the Motol University Hospital between 2010 and 2020 were retrospectively reviewed, and according to the absence or presence of extraosseous manifestations divided into two cohorts – bone limited CRMO and complex CRMO. The two groups were compared in terms of demographic data, age at disease onset, number and site of bone lesions, laboratory biomarker values, and need of escalation to a second-line therapy. Results Thirty-seven children (30 female, 7 male) with confirmed CRMO were included in the analysis. The mean age at disease onset was 10 years. All but 3 patients presented with multifocal disease. Twenty-three children (62%) had at least one extraosseous manifestation (13 sacroiliitis, 8 inflammatory bowel disease, 6 skin disease [acne, pustulosis, or psoriasis], 7 arthritis). Complex CRMO was associated with a significantly higher ESR rate (p = 0.0064) and CRP level (p = 0.018). The groups did not differ in number of foci or in age at disease onset. Bone lesion distribution differed between the two groups with significantly more frequent involvement of clavicle (p = 0.011) and pelvis (p = 0.038) in patients with complex CRMO. Children with complex CRMO more often needed escalation of therapy to DMARDs and biologic agents. Conclusion Our data suggest that CRMO affecting solely the skeleton has milder course compared to complex CRMO with extraskeletal features. Further studies are needed to explore the clinical as well as the patient reported outcomes and promote individually tailored therapeutic strategies in both CRMO phenotypes.

Abstract Objectives The objectives were to assess changes in radiological disease activity in children with chronic non-bacterial osteomyelitis (CNO) receiving pamidronate therapy and to test a modified radiological index for non-bacterial osteitis (mRINBO) in CNO. mRINBO was used for standardized reporting and quantification of whole-body MRI (WBMRI) findings resulting in an individual summary patient score. Methods WBMRI was retrospectively assessed in 18 children with CNO at baseline and after receiving pamidronate therapy for one year. Parameters of interest were: number and anatomic site of radiologically active bone lesions (RAL), size of RAL, extramedullary affection, spinal involvement and changes in mRINBO, which includes both the number and maximal size of RAL (RALmax) in addition to extramedullary and chronic changes. Results At the time of diagnosis, the mean age of the children was 9.8 (sd, 8.7–10.9) years and 11/18 were females. The number of RALs per patient decreased from median [interquartile range] 4.5 [3–8] to 3 [2–5] RALs per patient (p = 0.02) and extramedullary inflammatory changes regressed. Sixty-one percent of all RALs occurring at baseline resolved and three children became without active inflammatory lesions by WBMRI. The median size of RALs did not change when taking new lesions occurring in 7/18 children into account, but RALmax decreased significantly from 39 [29–45] mm at baseline to 28 [20–40] mm (p

Abstract Background Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis, is a noninfectious autoinflammatory disorder that occurs primarily in children and adolescents and is characterized by episodic musculoskeletal pain with a protracted course. Main body Traditionally, the diagnosis of CNO is made by exclusion and commonly requires bone biopsy to rule out infection and malignancy. However, bone biopsy may be avoided when imaging and clinical characteristic features are present, such as multifocal bone lesions at typical sites, no constitutional symptoms and no signs of infection in laboratory test results. Whole-body magnetic resonance imaging (WB-MRI) can assess signs of acute and chronic inflammation and enables the detection of CNO typical patterns of lesion location and distribution, thereby helping to exclude differential diagnosis. The goal of the present study paper is to review the main clinical and imaging aspects of the disease with emphasis on the role of WB-MRI in the diagnosis, assessment of disease burden and follow-up monitoring. Conclusion Radiologists need to be familiar with the imaging features to suggest the diagnosis as the early therapy may help to avoid irreversible secondary damage of skeletal system.

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]

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory disorder resulting from the multifocal bone and bone marrow lesions with periodic relapses and remissions and with an uncertain prognosis. Treatment options in CRMO are based on expert opinion and relatively small groups of patients. A nine-year-old female patient with no significant past medical history presented with compression fractures and multifocal bone lesions in the thoracic and lumbar spine, as shown in imaging (CT, MRI). Densitometry revealed a diffuse decrease in bone density. Based on the patient's clinical image and above examinations, the other possible aetiologies—infectious (including tuberculosis), neoplasms, Langerhans cell histiocytosis—were ruled out, which led to eventual final diagnosis—CRMO. The patient was successfully treated with pamidronate infusion initiated in cycles over three consecutive days every 3 months. In addition to clinical improvement, there was a significant remission of inflammation and bone structure healing assessed by MRI after four treatment cycles. Intravenous bisphosphonates usage seems to be a good therapeutic option in CRMO paediatric patients with spinal localization of the lesions complicated by compressive fractures. However, more data, based on larger patient populations, are needed to provide a detailed paediatric CRMO treatment algorithm. [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.

Objective: To evaluate the correlation between the clinical course of chronic recurrent multifocal osteomyelitis (CRMO) lesions and their imaging characteristics on follow-up MRIs. Material and Methods: Two musculoskeletal fellowship-trained radiologists retrospectively reviewed the initial and follow-up MRI images of 9 CRMO patients who were treated in our institution from 2008 to 2018. Evaluation of clinical course was based on symptomatology, lab results and physical examination and was compared to MRI findings, on follow-up MRIs. Results: Thirty-five CRMO lesions in 9 patients were identified. Patient’s ages ranged from 4 to 15 years with a mean age of 10 years (S.D.±3.22). Six of the 9 patients were female. Only 21 of 35 lesions had been longitudinally followed by MRI. Of the 39 follow-up MRI exams, there was clinical improvement 15 times, and 24 times there was no clinical improvement confirmed by the clinician. Three MRI features: 1) bone marrow edema (BME) size, 2) BME signal intensity and 3) periosteal edema, significantly correlated with the clinical course (p-value

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory disease, clinically characterized by chronic and recurrent episodes of osteoarticular inflammation, that generally presents in children and adolescents. From a dermatological point-of-view, CMRO can be associated with skin rashes mainly including psoriasis, palmoplantar pustulosis and acne. Pyoderma gangrenosum (PG) is a rare immune-mediated inflammatory skin disease classified within the spectrum of neutrophilic dermatoses that, in some cases, has been reported as cutaneous manifestation in CMRO patients. This paper presents a 16-year female patient diagnosed with CMRO, who presented PG lesions located on the lower leg, that arose after the administration of the tumour necrosis factor (TNF)-α inhibitor adalimumab. Cases of PG have been reported in patients being treated with certain medications, including TNF-α antagonists, leading to classified them in a setting aptly termed “drug-induced PG.” In this paper, we discuss the co-occurrence of PG and CRMO, in the light of recent evidence on the pathogenesis of both diseases and giving ample space to a literature review on drug induced PG. In our case, it is plausible that PG could be considered a cutaneous manifestation of CRMO, although the mechanisms underlying this intriguingly relationship remain to be fully unraveled.

PurposeOsteomyelitis is a group of bone infectious (bacterial osteomyeilitis—BO) and noninfectious inflammatory diseases (nonbacterial osteomyelitis—NBO) with similar clinical, radiology, and laboratory features. Many patients with NBO are misdiagnosed as BO and receive unnecessary antibiotics and surgery. Our study aimed to compare clinical and laboratory features of NBO and BO in children, to define key discriminative criteria, and to create an NBO diagnostic score (NBODS).MethodsThe retrospective multicenter cohort study included clinical, laboratory, and instrumental information about histologically confirmed NBO (n = 91) and BO (n = 31). The variables allowed us to differentiate both conditions used to construct and validate the NBO DS.ResultsThe main differences between NBO and BO are as follows: onset age—7.3 (2.5; 10.6) vs. 10.5 (6.5; 12.7) years (p = 0.03), frequency of fever (34.1% vs. 90.6%, p = 0.0000001), symptomatic arthritis (67% vs. 28.1%, p = 0.0001), monofocal involvement (28.6% vs. 100%, p = 0.0000001), spine (32% vs. 6%, p = 0.004), femur (41% vs. 13%, p = 0.004), foot bones (40% vs. 13%, p = 0.005), clavicula (11% vs. 0%, p = 0.05), and sternum (11% vs. 0%, p = 0.039) involvement. The following four criteria are included in the NBO DS: CRP ≤ 55 mg/l (56 points), multifocal involvement (27 points), femur involvement (17 points), and neutrophil bands ≤ 220 cell/μl (15 points). The sum > 17 points allowed to differentiate NBO from BO with a sensitivity of 89.0% and a specificity of 96.9%.ConclusionThe diagnostic criteria may help discriminate NBO and BO and avoid excessive antibacterial treatment and surgery.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease occurring mainly in the pediatric age group (before 16 years) and generally presents as a separate entity. Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome combines osteoarticular and cutaneous involvement, similar to CRMO, and falls into the spectrum of spondyloarthritis (SpA). The fact that a patient can progress from one disease to another raises the question of whether CRMO, like SAPHO, could fall within the spectrum of SpA, ranging from a predominantly osteoarticular form to an enthesitic form with more or less marked skin involvement. In this review, we set out to discuss this hypothesis by highlighting the differences and similarities between CRMO and juvenile SpA in clinical, radiological and pathophysiological aspects. A common hypothesis could potentially consider intestinal dysbiosis as the origin of these different inflammatory diseases. Interindividual factors such as gender, environment, genetics and/or epigenetic background could act as combined disease modifiers. This is why we suggest that pathophysiology, rather than clinical phenotype, be used to reclassify these diseases. [ABSTRACT FROM AUTHOR]

Introduction: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is an autoinflammatory bone disorder with predominantly paediatric onset. Children present with multifocal osteolytic lesions accompanied by bone pain and soft tissue swelling. Patients often exhibit extraosseous co-morbidities such as psoriasis, inflammatory bowel disease, and arthritis. Objectives: Comparison of children with two different phenotypes of CRMO defined by presence or absence of extraosseous co-morbidities. Methods: Children diagnosed with CRMO at the Motol University Hospital between 2010 and 2020 were retrospectively reviewed, and according to the absence or presence of extraosseous manifestations divided into two cohorts – bone limited CRMO and complex CRMO. The two groups were compared in terms of demographic data, age at disease onset, number and site of bone lesions, laboratory biomarker values, and need of escalation to a second-line therapy. Results: Thirty-seven children (30 female, 7 male) with confirmed CRMO were included in the analysis. The mean age at disease onset was 10 years. All but 3 patients presented with multifocal disease. Twenty-three children (62%) had at least one extraosseous manifestation (13 sacroiliitis, 8 inflammatory bowel disease, 6 skin disease [acne, pustulosis, or psoriasis], 7 arthritis). Complex CRMO was associated with a significantly higher ESR rate (p = 0.0064) and CRP level (p = 0.018). The groups did not differ in number of foci or in age at disease onset. Bone lesion distribution differed between the two groups with significantly more frequent involvement of clavicle (p = 0.011) and pelvis (p = 0.038) in patients with complex CRMO. Children with complex CRMO more often needed escalation of therapy to DMARDs and biologic agents. Conclusion: Our data suggest that CRMO affecting solely the skeleton has milder course compared to complex CRMO with extraskeletal features. Further studies are needed to explore the clinical as well as the patient reported outcomes and promote individually tailored therapeutic strategies in both CRMO phenotypes. [ABSTRACT FROM AUTHOR]

Aim: Telomeres are DNA sequences of tandem TTAGGG repeats that protect chromosome ends from degradation and instability. Constitutional loss‐of‐function telomerase mutations result in rapid telomere shortening, premature senescence and cell death. Liver cirrhosis is rare and has only been reported in adults. We present five family members of Bedouin‐Muslim origin, all of which carry the same mutation, and yet demonstrate an extremely variable phenotypical presentation, including liver cirrhosis during early childhood. Methods: A multidisciplinary long‐term follow‐up of two healthy and three affected patients was analysed. The mutation (r.95G>C) was identified in all patients using Sanger sequencing. Telomere length samples were obtained and analysed. Results: Clinical phenotypes were extremely variable, including age at first symptoms, organ involvement, disease severity and patient prognosis. The most prominent clinical phenotype is liver involvement, including end‐stage liver disease early in life, which affects three members of the family. Affected patients had markedly shorter telomeres. Conclusion: We describe an unusual presentation of early liver failure in telomere disease patients. Little, if any, is known about the association between the genotype and phenotype among children with telomere disease and whether the mutation we have described (r.95G>C) is predisposed to early severe hepatic involvement. [ABSTRACT FROM AUTHOR]

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

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

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.

Chronic recurrent multifocal osteomyelitis is a rare, multisystemic inflammatory disease that affects children and adolescents. We present the case of an African‐American adolescent male who presented with recurrent swelling of the temporal region with skull involvement on head imaging, which is atypical for chronic recurrent multifocal osteomyelitis. He had clinical and laboratory improvement after initiation of indomethacin and pamidronate. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory disease characterised by sterile bone lesions. We report a case of a seven-year-old female patient who presented at a university hospital in 2010 and 2018 with CRMO. While the most promising results have been observed in patients under treatment with bisphosphonates (BPs), the initial decision to treat the current patient with a dose of zoledronic acid every six months was recalled as the patient developed tonic-clonic seizures immediately following the second dose BP administration. Following recall, the patient maintained a prompt response at follow-up and her disease remained controlled with non-steroidal anti-inflammatory drugs. The current case report speculates a possible relationship between BP use and a possible seizure threshold reduction, thereby emphasising the need for closer monitoring when BPs are used. [ABSTRACT FROM AUTHOR]

Background: Chronic recurrent multifocal osteomyelitis (CRMO) is a diagnosis of exclusion, relying heavily on whole-body magnetic resonance imaging (WB-MRI) for diagnosing and evaluating response to therapy. Information with respect to disease distribution and imaging correlation with clinical disease severity at initial presentation is lacking. Objective: To retrospectively characterize distribution of disease on WB-MRI and to correlate imaging findings with disease severity at initial rheumatology presentation. Materials and methods: Using a modified version of a recently devised imaging-based scoring system, we evaluated disease distribution and correlation between findings on WB-MRI and clinical disease severity in 54 patients presenting for initial evaluation of CRMO. Symptomatic lesion sites were extracted from chart review and physician global assessment was determined by the consensus of two rheumatologists. Results: Sites of CRMO involvement evident on imaging at initial presentation had a strong predilection for the pelvis and lower extremities. There was significant correlation between the number of lesions detected on WB-MRI and total clinical severity score at initial rheumatology presentation (P<0.01). However, no other imaging parameter correlated with disease severity. Conclusion: While the overall number of lesions identified on MRI correlates with clinical severity scores at initial imaging, other MR parameters of CRMO lesions may not be reliable indicators of disease severity at initial presentation. Further research is needed to assess whether these parameters are implicated in longitudinal disease severity or overall response to therapy. [ABSTRACT FROM AUTHOR]

Background: Chronic recurrent multifocal osteomyelitis (CRMO) is a bone inflammatory disorder characterized by osteolytic, usually multiple, symmetric lesions. Diagnosis is one of exclusion, and no standardized therapies are available. Presumed deregulation of the interleukin (IL)‐1β axis, as observed in 2 monogenic autoinflammatory conditions such as Majeed syndrome (LPIN2 mutations) and deficiency of IL‐1 receptor antagonist (IL1RN mutations) with CRMO‐like bone involvement, suggests the blockade of IL‐1 as potentially useful also in this condition, even if scarce data are available. Case presentation: We report the case of a 13‐year‐old girl affected by a multidrug‐resistant and pyoderma gangrenosum‐complicated CRMO treated with canakinumab, a human monoclonal antibody targeting IL‐1β. Conclusion: In this young patient pyoderma gangrenosum and CRMO showed a rapid and satisfactory response to canakinumab, although over time a decreased efficacy in controlling bone disease was observed. [ABSTRACT FROM AUTHOR]

Objectives: The objectives were to assess changes in radiological disease activity in children with chronic non-bacterial osteomyelitis (CNO) receiving pamidronate therapy and to test a modified radiological index for non-bacterial osteitis (mRINBO) in CNO. mRINBO was used for standardized reporting and quantification of whole-body MRI (WBMRI) findings resulting in an individual summary patient score. Methods: WBMRI was retrospectively assessed in 18 children with CNO at baseline and after receiving pamidronate therapy for one year. Parameters of interest were: number and anatomic site of radiologically active bone lesions (RAL), size of RAL, extramedullary affection, spinal involvement and changes in mRINBO, which includes both the number and maximal size of RAL (RALmax) in addition to extramedullary and chronic changes. Results: At the time of diagnosis, the mean age of the children was 9.8 (sd, 8.7–10.9) years and 11/18 were females. The number of RALs per patient decreased from median [interquartile range] 4.5 [3–8] to 3 [2–5] RALs per patient (p = 0.02) and extramedullary inflammatory changes regressed. Sixty-one percent of all RALs occurring at baseline resolved and three children became without active inflammatory lesions by WBMRI. The median size of RALs did not change when taking new lesions occurring in 7/18 children into account, but RALmax decreased significantly from 39 [29–45] mm at baseline to 28 [20–40] mm (p < 0.01) at year-one with a concomitant decrease of mRINBO from a median of 5 [4–7] to 4 [3–5] (p = 0.05). Conclusions: Pamidronate therapy resulted in a decrease of mRINBO from baseline to year one. mRINBO may be a potential scoring method to quantify changes in radiological disease activity in children with CNO. However, further studies are needed to test feasibility and validity of mRINBO. [ABSTRACT FROM AUTHOR]

Background: Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis, is a noninfectious autoinflammatory disorder that occurs primarily in children and adolescents and is characterized by episodic musculoskeletal pain with a protracted course. Main body: Traditionally, the diagnosis of CNO is made by exclusion and commonly requires bone biopsy to rule out infection and malignancy. However, bone biopsy may be avoided when imaging and clinical characteristic features are present, such as multifocal bone lesions at typical sites, no constitutional symptoms and no signs of infection in laboratory test results. Whole-body magnetic resonance imaging (WB-MRI) can assess signs of acute and chronic inflammation and enables the detection of CNO typical patterns of lesion location and distribution, thereby helping to exclude differential diagnosis. The goal of the present study paper is to review the main clinical and imaging aspects of the disease with emphasis on the role of WB-MRI in the diagnosis, assessment of disease burden and follow-up monitoring. Conclusion: Radiologists need to be familiar with the imaging features to suggest the diagnosis as the early therapy may help to avoid irreversible secondary damage of skeletal system. [ABSTRACT FROM AUTHOR]

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease that predominantly affects children and adolescents. Currently, CRMO diagnoses are based on a combination of clinical, radiological, pathological, and longitudinal findings. However, distinguishing CRMO from malignant bone tumors using imaging is occasionally challenging. Fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging characteristics in CRMO (specifically, the maximum standardized uptake value (SUVmax)) have been described previously. The lesions exhibited increased FDG uptake despite the benign nature of the disease; the SUVmax was notably high (4.90). These findings suggest that FDG/PET plays a limited role in the differential diagnosis of CRMO., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hirota et al.)

We present a 9-year-old girl with persistent pain and swelling of the left wrist. X-ray, magnetic resonance imaging (MRI) and bone biopsy led to the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO), affecting phalangeal and metacarpal bases and distal carpal bones on the ulnar side of the wrist. She was treated with non-steroidal anti-inflammatory drugs and complete remission with no long-term sequelae was achieved. CRMO is a rare auto-inflammatory condition with infrequent involvement of the hand. The current literature is discussed. The aim of this report is to raise awareness of the condition to reduce the time to diagnosis and unnecessary antibiotic treatment and to prevent permanent disability due to the progression of the disease. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

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.