Diagnosis Of Chronic Nonbacterial Osteomyelitis Research Articles

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

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

СЛОЖНОСТИ ДИАГНОСТИКИ ХРОНИЧЕСКОГО НЕБАКТЕРИАЛЬНОГО ОСТЕОМИЕЛИТА У ДЕТЕЙ

The article presents up-to-date data concerning etiopathogenesis, clinical manifestations and diagnosis of chronic non-bacterial osteomyelitis in children. Chronic relapsing multifocal osteomyelitis (CRMO) is a rare condition with unknown etiology, which is characterized by presence of numerous relapsing focuses of bone destruction. Diagnostic work-up for CRMO includes magnetic resonance imaging (MRI) and bone scintigraphy, blood culture and bone biopsy. The diagnosis of CRMO can be made if negative results of blood culture and bone biopsy material are observed and bone malignancy and infection are ruled out. Main therapeutic approaches and follow-up are given in the article. Clinical case of CRMO in combination with juvenile idiopathic arthritis (JIA) in a ten year old boy is described. CRMO should be considered and differential diagnosis should be done in cases of atypical course of JIA especially in those with absence of specific immunological markers.

First-year follow-up of children with chronic nonbacterial osteomyelitis\u2014an analysis of the German National Pediatric Rheumatologic Database from 2009 to 2018

ObjectiveTo assess the first-year features of patients with chronic nonbacterial osteomyelitis (CNO).MethodsPatients 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.ResultsOf 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.ConclusionTo 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 registrationNot applicable.

Chronic nonbacterial osteomyelitis: report of thirteen cases

Introduction: Chronic Nonbacterial Osteomyelitis (CNO), also known as Chronic Recurrent Multifocal Osteomyelitis (CRMO), is a rare autoinflammatory bone disorder that causes multifocal or unifocal aseptic lytic lesions in bone biopsy and is characterized by periodic exacerbations and remissions of sterile osteomyelitis. The aim of this report was to describe clinical features, subsidiary exams, treatment and outcome of thirteen cases of CNO followed in a tertiary center in Brazil. Methods: We carried out a single-center retrospective descriptive review of clinical records, including thirteen children and adolescents with CNO followed between 2010 and 2020 in our tertiary service in Brazil. Medical records were reviewed in order to collect data about clinical presentation, inflammatory markers, radiological and histological findings, treatment and outcome.The diagnosis of CNO was based on the Bristol diagnostic criteria for CRMO. Results: Thirteen patients were included in this study, of whom 46% were female. Median of current age and of follow-up time were 11 years (range 8.5-20.4) and 40 months (range 9-123), respectively. Median age at disease onset was 8.1 years (range 0.8–15.3) and median age at diagnosis was 11 years (range 7-16.1). The most affected sites were metaphysis and diaphysis of long bones. Median number of initially affected bones was 4.0 (range 1-7). Five patients had recurrences. All patients had increased acute phase reactants at disease onset. All patients had at least one of the characteristic findings on MRI (lytic lesions, osteitis, hyperostosis and periostitis). Five patients received systemic glucocorticoids, eight received methotrexate and seven received bisphosphonates (alendronate). Conclusion: The awareness of the features of CNO is important for an early diagnosis and may avoid unnecessary diagnostic procedures and prolonged antibiotic therapies.

Chronic nonbacterial osteomyelitis: single center experience

Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory disease from the group of multifactorial diseases. It is characterized by non-infectious recurrent bone lesions, usually manifesting in childhood. The aim of this study was to analyze the clinical, laboratory, radiological and histological data of 33 patients (12 boys, 21 girls) with a diagnosis of chronic nonbacterial osteomyelitis. This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. 25/33 patients were hospitalized to the Center with suspected neoplastic disease bone. The median age of CNO manifestation was 9.6 years. 24/33 had a multi-focal form of the disease. 5 patients had fever. Nonsteroidal anti-inflammatory drugs were the first therapy for all patients, achieving clinical remission in 4 cases. Zoledronic acid were used in 29 patients with remission in 19, adalimumab in 10 patient with remission in 9. In one patient stabilization was achieved only with the combination of methotrexate and canakinumab therapy.

Chronic nonbacterial osteomyelitis : Imaging and differential diagnoses

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease in childhood and adolescence with apreference for the female gender. It is manifested with multiple osseous lesions, with a predilection for the metaphyseal end zones of the long bones of the lower extremities. These bone lesions usually occur multifocally, can recur and develop a different appearance depending on the bone structure affected. Patients present with alonger disease history, changing clinical symptoms and unspecific paraclinical signs. Magnetic resonance imaging (MRI) is the imaging of choice and particularly as awhole body examination can speed up the diagnosis and is an important component of follow-up controls. Differential diagnoses include numerous inflammatory, benign and malignant bone diseases. Therefore, it is essential to know the diagnosis of CNO and to take it into consideration in cases of an unclear inflammatory bone process in young patients.

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Proceedings From the Clinical and Scientific Innovations in Oral and Maxillofacial Surgery Conference 2019

Chronic non-bacterial osteomyelitis of clavicle

The patient was a 10-year-old girl with pain and swelling of the left clavicle. The physical examination was normal except swelling and tenderness of the left clavicular region. All the...

Use of infliximab in patient with chronic non-bacterial osteomyelitis, case report

Introduction: chronic non-bacterial osteomyelitis (CNO) is a non-infectious inflammatory of unknown etiology. Case description: ABA, female, 16 years old, was admitted with a pain in her left thigh. At the time, it was suspected to be caused by a tumor, and a bone scintigraphy was requested, which evidenced a focal area of increased uptake in the distal metadiaphyseal area of the left femur. A bone biopsy was performed, and its result was compatible with chronic osteomyelitis. The patient started taking pamidronate (withdrawn due to treatment failure) and methotrexate (subsequently suspended due to urticarial reaction). After some years of clinical stability, a new focal area of osteomyelitis appeared, in the distal right femur. The use of anti-TNF (infliximab) was chosen, resulting in an improvement of the algic state. Discussion: the diagnosis of CNO is made by process of elimination and is based on clinical, laboratorial, radiological, bacteriological and histological data. Non-hormonal anti-inflammatory and bisphosphonate drugs are recommended as initial therapy. Disease-modifying drugs, steroids and anti-TNFα have been used in severe and recurring cases. Conclusion: the authors present a CNO case with good response to anti-TNFα after treatment failure with bisphosphonates.

Serum Interleukin-6 and CCL11/Eotaxin May Be Suitable Biomarkers for the Diagnosis of Chronic Nonbacterial Osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO), the most severe form of chronic nonbacterial osteomyelitis (CNO), is an autoinflammatory bone disorder. In the absence of diagnostic criteria or biomarkers, CNO/CRMO remains a diagnosis of exclusion. The aim of this study was to identify biomarkers for diagnosing multifocal disease (CRMO). Sera from 71 pediatric CRMO patients, 11 patients with osteoarticular infections, 62 patients with juvenile idiopathic arthritis (JIA), 7 patients with para-infectious or reactive arthritis, and 43 patients with acute leukemia or lymphoma, as well as 59 healthy individuals were collected. Multiplex analysis of 18 inflammation- and/or bone remodeling-associated serum proteins was performed. Statistical analysis included univariate ANOVA, discriminant analysis, univariate receiver operating characteristic (ROC) analysis, and logistic regression analyses. For 14 of 18 blood serum proteins, significant differences were determined between CRMO patients, at least one alternative diagnosis, or healthy controls. Multi-component discriminant analysis delivered five biomarkers (IL-6, CCL11/eotaxin, CCL5/RANTES, collagen Iα, sIL-2R) for the diagnosis of CRMO. ROC analysis allowed further reduction to a core set of 2 biomarkers (CCL11/eotaxin, IL-6) that are sufficient to discern between CRMO, healthy controls, and alternative diagnoses. Serum biomarkers CCL11/eotaxin and IL-6 differentiate between patients with CRMO, healthy controls, and alternative diagnoses (leukemia and lymphoma, osteoarticular infections, para-infectious arthritis, and JIA). Easily accessible biomarkers may aid in diagnosing CRMO. Further studies testing biomarkers in larger unrelated cohorts are warranted.

Serum biomarkers for the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO)

Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Chronic recurrent multifocal osteomyelitis (CRMO) is the most severe form of CNO. It is characterized by recurring episodes of bone inflammation that can last for years and may cause chronic pain, pathological fractures, and disability. Despite recent advances in targeting disease mechanisms, the exact pathophysiology of CNO/CRMO remains unknown. Diagnosis of CNO can be challenging, because symptoms tend to be mild and highly variable, and is further complicated by the absence of widely accepted diagnostic criteria and disease biomarkers.

Chronic nonbacterial osteomyelitis in children: a retrospective multicenter study.

BackgroundTo determine the clinical presentation, current treatment and outcome of children with nonbacterial inflammatory bone disease.MethodsRetrospective multicenter study of patients entered into the Swiss Pediatric Rheumatology Working Group registry with a diagnosis of chronic nonbacterial osteomyelitis (CNO) and synovitis acne pustulosis hyperostosis osteitis (SAPHO) syndrome. The charts were reviewed for informations about disease presentation, treatment, course and outcome.ResultsForty-one children (31 girls and 10 boys) from 6 pediatric hospitals in Switzerland diagnosed between 1995 and 2010 were included in the study. The diagnosis was multifocal CNO (n = 33), unifocal CNO (n = 4) and SAPHO syndrome (n = 4). Mean age at onset of CNO was 9.5 years (range 1.4–15.6) and mean follow-up time was 52 months (range 6–156 months). Most patients (n = 27) had a chronic persistent disease course (>6 months), 8 patients had a course with one or more relapses and 6 patients had only one episode of CNO. Forty nine percent had received at least one course of antibiotics. In 57 % treatment with nonsteroidal anti-inflammatory drugs (NSAID) was sufficient to control the disease. Twelve out of 16 children with NSAID failure subsequently received corticosteroids, methotrexate, TNF α inhibitors, bisphosphonates or a combination of these drugs.ConclusionsIn a multicenter cohort of 41 children 22 % started with unifocal lesion with a significant diagnostic delay. A higher proportion presented with chronic persistent disease than with a recurrent form. An osteomyelitis in the pelvic region is significantly associated with other features of juvenile spondylarthritis.

Chronic nonbacterial osteomyelitis in children

Chronic Nonbacterial Osteomyelitis (CNO) is an autoinflammatory disease that presents as recurrent flares of bone pain, sometimes febrile and with lytic radiological pictures. Extraarticular manifestations are also possible. We present a retrospective study of eleven children (ten females, one male), followed in Pediatric Orthopedic ward of the Caen University Hospital between 2001 and 2011. We report the initial symptoms, the biological profiles and the radiological findings which led to the diagnosis of CNO. Secondly, we describe treatment and disease’s evolution of these patients. The mean age at CNO onset in our study was 10.5 years (4 to 14). Girls were affected more than boys (10/1). The mean term to the diagnosis was ten months (one week to five years). The most suggestive feature was the involvement of the metaphyses of the long bone (tibia and femur), but all bones could be involved (table ​(table1).1). Eight patients underwent a bone biopsy. Eleven patients had a radionuclide bone scanning, with asymptomatic lesions detected. Table 1 bone involvement at the CNO onset and at the end of follow-up At the end of the follow-up, the involvement of the spine is more frequent than at diagnosis (table​(table1).1). Five patients had an articular involvement, before the CNO onset, or later in the evolution. One patient had a palmoplantar pustulosis, and one a psoriasis. Only six patients had an increased C-reactive protein level, and seven an increased erythrocyte sedimentation rate at the CNO onset. All are treated by NSAIDs: seven children had regular attacks of pain, four were in remission. Two patients had an inequal length of inferior limbs, and two patients had vertebral deformities. In conclusion, the patients of our study had the same characteristics as patients in the literature. A better comprehension of the physiopathology seems to classify CNO as auto-inflammatory diseases, even though some patients evolve into spondylarthropathy.

Chronic multifocal non-bacterial osteomyelitis in hypophosphatasia mimicking malignancy

BackgroundHypophosphatasia (HP) is characterized by a genetic defect in the tissue-nonspecific alkaline phosphatase (TNSALP) gene and predominantly an autosomal recessive trait. HP patients suffer from reduced bone mineralization. Biochemically, elevated concentrations of substrates of TNSALP, including pyridoxal-5'-phosphate and inorganic pyrophosphate occur in serum, tissues and urine. The latter has been associated with chronic inflammation and hyperprostaglandinism.Case presentationWe report on 2 affected children presenting with multifocal inflammatory bone lesions mimicking malignancy: A 6 years old girl with short stature had been treated with human growth hormone since 6 months. Then she started to complain about a painful swelling of her left cheek. MRI suggested a malignant bone lesion. Bone biopsy, however, revealed chronic inflammation. A bone scan showed a second rib lesion. Since biopsy was sterile, the descriptive diagnosis of chronic non-bacterial osteomyelitis (CNO) was established. The diagnostic tests related to growth failure were repeated and subsequent analyses demonstrated a molecular defect in the TNSALP gene. The second girl (10 years old) complained about back pain after she had fallen from her bike. X rays of her spine revealed compressions of 2 thoracic vertebrae. At first these were considered trauma related, however a bone scan did show an additional lesion in the right 4th rib. A biopsy of this rib revealed a sterile lympho- plasmocytoid osteomyelitis suggesting multifocal CNO. Further analyses did show a decreased TNSALP in leukocytes and elevated pyridoxal phosphate in plasma, suggesting a heterozygous carrier status of HP.ConclusionChronic bone oedema in adult HP and chronic hyper-prostaglandinism in childhood HP do suggest that in some HP patients bone inflammation is present in conjunction with the metabolic defect. Sterile multifocal osteomyelitis could be demonstrated. Non-steroidal anti-inflammatory treatment achieved complete remission. These cases illustrate chronic inflammation of the bone as a new feature of HP.