Autoinflammatory Bone Disorder Research Articles

Chronic Non-bacterial Osteomyelitis (CNO) In Childhood: A Review.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Although it is considered a rare disease, CNO is likely to be the single most common autoinflammatory bone disease in childhood, underdiagnosed and underreported due to a lack of awareness of the condition in both medics and patients and the absence of validated diagnostic criteria. The exact underlying pathogenesis of CNO remains unknown, making targeted treatment difficult. This issue is exacerbated by the lack of any randomised control trials, meaning that treatment strategies are based solely on retrospective reviews and case series. This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

Chronic Noninfectious Osteomyelitis: A Review of Imaging Findings

AbstractChronic noninfectious osteomyelitis or chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis, is an autoinflammatory bone disorder primarily affecting the pediatric age group. Currently, it is diagnosed on the basis of clinical, laboratory, and imaging features. Imaging plays a crucial role in the diagnosis and follow-up of CNO with whole body magnetic resonance imaging (WBMRI) being the main modality. Radiographs assist in exclusion of common differential diagnoses like infections and malignancy. WBMRI aids in disease detection and exclusion of differential diagnoses, identifies additional lesions, and has a role in ascertaining the pattern of bony involvement which helps with prognostication and grading. Recent recognition of specific morphological and distribution patterns on WBMRI is increasingly allowing an upfront diagnosis of this entity to be made on imaging alone. It is also helpful for assessment of response to therapy during follow-up. This review aims to summarize the role of imaging in the evaluation of CNO, with special emphasis on WBMRI in its assessment.

Chronic recurrent multifocal osteomyelitis: Case report and review of the literature.

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare inflammatory disease. This report aims to analyze the clinical characteristics of CRMO and enhance clinicians' comprehension. We present 3 atypical cases, highlighting their unique clinical features, diagnostic challenges, and effective treatment strategies. We retrieved 3 CRMO cases in our hospital from September 2019 to August 2022. The clinical features were analyzed retrospectively, and relevant literatures were reviewed. All 3 cases initially presented with bone pain, normal leucocyte counts, negative rheumatoid factors and no signs of sclerotic or hyperostotic lesions. Case 1, a 12-year-old girl, exhibited concurrent acne on the forehead and historic necrotizing lymphadenitis, a previously unreported association with CRMO. Case 2, a 14-year-old boy, tested positive for human leukocyte antigen-B27 and displayed scoliosis along with multifocal osteomyelitis. Case 3, a 9-year-old girl, presented with scoliosis, and chest computed tomography revealed changes in the T8 vertebral body, initially suggesting Langerhans cell histiocytosis. Bone biopsy was conducted in case 1 and case 3, revealing chronic inflammation. All 3 cases affected long bones, pelvis, and vertebra, involving 8, 6 and 5 bones, respectively, identified by magnetic resonance imaging. Genetic analysis was undertaken in cases 1 and 2 but no pathogenic mutations were identified. Upon the confirmation of a CRMO diagnosis, all patients were initiated on a treatment regimen comprising nonsteroidal anti-inflammatory drugs and tumor necrosis factor-α inhibitors. In cases 1 and 2, due to the severity of their bone pain, they were also administered to disease-modifying anti-rheumatic drugs, specifically methotrexate. All 3 patients achieved remission of bone pain. To gain a more comprehensive understanding of CRMO, we conducted a thorough review of relevant literature. CRMO is a rare autoinflammatory bone disorder with diverse clinical presentations and a lack of specific laboratory tests, which leads to potency to misdiagnosis or delayed diagnosis. By raising awareness and improving diagnostic criteria, physicians are now better equipped to identify CRMO. We contribute to share our understanding of CRMO by presenting 3 cases with untypical clinical features, highlighting the importance of recognizing this rare condition for timely and effective management.

Chronic Osteomyelitis of Clavicle as a Primary Manifestation of CRMO in an Adolescent: A Case Report

Background: Chronic recurrent multifocal osteomyelitis (CRMO) is an auto-inflammatory bone disorder characterized by aseptic, mono- to multi-focal inflammation of the bones, yet its etiology remains undetermined. Diagnosis of CRMO is often challenging due to its overlapping signs and symptoms with other bone disorders, leading to potential long-term deformities. Increasing awareness of the various presentations of CRMO is crucial for timely diagnosis and management. Case presentation: A 14-year-old girl presented to our center with recurrent left clavicle pain, persisting for more than 3 years before referral. She had received multiple courses of analgesics. Physical examination revealed a hard, fixed mass in the medial third of the left clavicle, painless to palpation, with no inflammatory signs. MRI showed diffuse multiple hypo-signal lesions of the medial third of the left clavicle, blowing the bone cortex with infiltration of the soft tissues. Differential diagnoses were ruled out through bone biopsy, and laboratory tests. The patient responded favorably to treatment with Methotrexate, and Indomethacin, with no relapse observed during one year of follow-up. Conclusions: Uncommon presentations of CRMO can pose challenges in diagnosis, potentially leading to prolonged diagnostic processes. Increasing awareness among specialists regarding these presentations can facilitate earlier diagnosis and more effective treatment of CRMO patients.

Geriatric chronic recurrent multifocal osteomyelitis (CRMO) mimicking multifocal multiple myeloma: a first in an octogenarian

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.

P383 Chronic Recurrent Multifocal Osteomyelitis associated with Paediatric Inflammatory Bowel disease: A Multi-Center Retrospective Study from the Paediatric IBD Porto Group of ESPGHAN

Abstract Background Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare, autoinflammatory bone disorder. CRMO was linked with inflammatory bowel disease (IBD), either as an extra intestinal manifestation or as a paradoxical effect of anti-TNFa therapy. Our goal was to define the clinical features and natural history of patients carrying a dual diagnosis of CRMO and IBD Methods Medical records of pediatric patients with a dual diagnosis of IBD and CRMO were reviewed in nineteen centers from the Paediatric IBD Porto Group of ESPGHAN. Collected data included demographic characteristics, disease features, laboratory studies, bone imaging findings and outcomes of each disease Results Forty five patients (21 [47%] females) with a diagnosis of CRMO and IBD (32 [71%] with Crohn’s disease) were included. Median age at the time of dual diagnosis was was 10.2 (IQR 12-13.5) years. Patients were divided into 3 groups, based on whether CRMO developed before, during or after IBD diagnosis. In 15 patients (33%), CRMO was diagnosed ±3 months from the time of IBD diagnosis, with 8 (53%) and 2 (13%) exhibiting mild and moderate-severe IBD activity, respectively. In 20 children (44%) IBD preceded CRMO diagnosis by >3 months with a median time of 238 (85-344) weeks. At the time of dual diagnosis, 12 (60%) patients were in IBD remission and 5 (25%) exhibited moderate-severe disease activity; however, CRP and ESR were elevated (1.5 [0.4-3.4] mg/dL and 35 [21-55] mm/h, respectively) while median fecal calprotectin was 567 (68-1800) mcg/gr, including 4 patients <100 mcg/gr. 17 patients (85%) were on anti-TNFa medication at the time CRMO developed. In 10 (22%) patients CRMO preceded the diagnosis of IBD (>3 months before IBD evolution) with a median time 46 (25-248) weeks. At time of IBD presentation, CRMO was in remission in 5 patients (50%). 4 patients were diagnosed with IBD, despite the lack of any abnormal gastro-intestinal symptoms. In patients in which CRMO was diagnosed after or during IBD diagnosis, different therapeutic regimens were used, including anti-TNFa agents, methotrexate, ustekinumab, NSAID’s and corticosteroids. Two patients also received bisphosphonates. In patients in which CRMO was diagnosed after or during IBD diagnosis, CRMO remission, defined as lack of bone pain, was achieved in 22.2 (15-51.8) weeks. CRMO complications occurred in 4 patients and included vertebral collapse, length discrepancy, bone fracture and bone deformity Conclusion In the largest cohort to date, CRMO presentation was not necessarily related to clinically active intestinal inflammation and could present before, during or after IBD diagnosis. CRMO remission was achieved in all patients; Nevertheless, a small number of patients developed significant bone complications

Chronic Recurrent Multifocal Osteomyelitis: A Challenging Diagnosis in The Pediatric Age Group and The Role of Imaging: Sharing A Rare Clinical Experience from Ethiopia, East Africa

Chronic recurrent multifocal osteomyelitis, which was originally described as chronic non-bacterial osteomyelitis is an autoinflammatory bone disorder of idiopathic origin affecting the metaphyseal portion of long bones at multiple sites. This disease entity, which was previously considered to be rare; is now showing a higher incidence according to recent studies. The disease affects children in the age range of 8-11 years and affects females more than males. It is characterized by clinical symptoms persisting more than six months with remissions and episodic exacerbations. Here we present a case of a 12- and half year-old girl who had multiple painful swellings with tenderness in her extremities and clavicle over a 4-year period which exacerbated over the last 18 months prior to diagnosis.

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

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

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

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

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

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

Chronic Nonbacterial Osteomyelitis and Inflammatory Bowel Disease: A Literature Review-Based Cohort.

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. 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. 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. 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.

Two phenotypes of chronic recurrent multifocal osteomyelitis with different patterns of bone involvement

IntroductionChronic 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.ObjectivesComparison of children with two different phenotypes of CRMO defined by presence or absence of extraosseous co-morbidities.MethodsChildren 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.ResultsThirty-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.ConclusionOur 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.

P43 A complicated road to diagnosis: Auto inflammatory bone disease

Introduction/BackgroundAuto inflammatory bone disorders are characterized by chronic non-infectious osteomyelitis and inflammation-induced bone resorption. It results from aberrant activation of components of the innate immune system. The auto inflammatory bone disorder includes chronic non-bacterial osteomyelitis (CNO) and its severe form chronic recurrent multifocal osteomyelitis (CRMO); synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome; Majeed syndrome; deficiency of interleukin-1 receptor antagonist (DIRA) and cherubism. The most common among this is CRMO/CNO. The disease can affect any part of the body but the metaphyseal region of the long bones, clavicle, and vertebra are the most commonly affected site.Description/MethodA 9 year old girl presented with five month history of swelling over right periocular and temporal region, associated with skin discoloration and difficulty in opening her eyes. She also reported headache more in the right frontal region. She had on and off exacerbations of skin discoloration and headaches. There was no history of fevers, weight loss, night sweats, skin lesions or arthritic symptoms. She did not have a personal or family history of inflammatory or autoimmune disorders. She is under ophthalmology elsewhere since the age of 3 months with a right divergent squint and history of right squint surgery at 6 years.Physical examination revealed swelling involving right infraorbital and temporal region, which was soft and not tender to touch with associated erythema in the same site. There were no signs of meningism or altered mental status. Musculoskeletal examination was unremarkable.Her blood test results showed mild increase in platelets (476 * 109), CRP 8mg/L, ESR (18mm/hr). IgG4 titres were mildly raised (1.16g/L). Other immunologic markers including rheumatoid factor, human leukocyte antigen B27, antinuclear antibody and anti-neutrophil cytoplasmic antibody were normal.Histopathological examination of bone and soft tissue of her right orbital rim showed low grade non-specific chronic inflammation with extensive appositional remodelling of bone suggestive of CRMO/SAPHO. No evidence of malignancy/infection.Later whole body MRI was performed to identify the extent of disease. MRI whole body was performed which showed multiple areas of bone marrow oedema and periostitis within the appendicular and axial skeleton, bilateral gluteal enthesitis and sacroilitis. There are some features that are atypical for CRMO (asymmetrical involvement, transphyseal involvement including epiphyseal involvement of the left humerus). Also noted to have right-sided periorbital oedema, oedema of the right masticator muscles and temporalis. Further planned to do dedicated MRI of left humerus with contrast.Discussion/ResultsIt can be difficult to consider what the problem is when a health care provider is presented with a group of seemingly disparate signs and symptoms with a history and time course that do not match classic (or commonly atypical) disease presentations. Common things happen commonly, so when symptoms occur without the usual co-occurring symptoms, unusual symptoms or time courses, it can be challenging.The current patient presented with periocular swelling with headache and skin discolouration. The differentials can be Langerhans cell histiocytosis, IgG4-related disease, osteoblastoma, and osteosarcoma. There were no hepatosplenomegaly, lymphadenopathy, also the mass was soft to palpate, and hence the above differentials were unlikely. Patient was initially evaluated at tertiary oncology centre and malignancy ruled out. The histopathology slides were reviewed and reported as mentioned above. In view of no skin manifestations, CRMO was the likely diagnosis considered. Hence MRI whole body performed.Barrani et al reported a similar type of unusual case of a 12-year-old girl with CRMO arising with recurrent episodes of left supraorbital headache, followed by the appearance of a periorbital dyschromia. Magnetic resonance imaging (MRI) of the skull and orbits revealed an important subacute inflammatory process. However, a few months later, the child presented a painful swelling of the left clavicle; the histological examination of the related biopsy allowed us to establish the diagnosis of CRMO.The follow up with our patient is quite a short duration and she might evolve later in the disease course giving more clarity!Key learning points/ConclusionIn evaluating a diagnostic dilemma, starting the laboratory evaluation helps to begin the process of trying to find an answer and can also help the families as “something is being done.”Chronic recurrent multifocal osteomyelitis can present with unifocal lesions, atypical locations or absence of recurrence.A high level of suspicion is paramount to avoid unnecessary biopsies and repeated antibiotic regimens.Families will often be quite concerned and support for them is also necessary and close communication and follow up is appropriate.

Presenting signs and clinical outcome in dogs with metaphyseal osteopathy: 39 cases (2009-2018).

To describe the presenting signs, concurrent conditions, treatment and outcome of dogs with metaphyseal osteopathy. Multi-centre retrospective review of medical records from January 2009 to September 2018 at four referral centres to identify dogs with a radiographic diagnosis of metaphyseal osteopathy. Thirty-nine dogs were identified. The median age at onset was 14 weeks old (range, 8 to 32 weeks old). There was a higher proportion of male dogs (29 of 39 male entire, nine of 39 female entire, one of 39 female neutered and no male neutered dogs). Where information was available, median time from the most recent vaccination was 20 days (range, 2 to 144 days). The most commonly recorded clinical signs were pyrexia (34 of 39), lethargy (32 of 39), pain (30 of 39), and being non-ambulatory (17 of 39). Thirty-five dogs required hospitalisation for analgesia and supportive care, 19 of 39 were discharged on prednisolone (median dose 2.0mg/kg/day; range, 0.9 to 2.6mg/kg/day), 18 of 39 were discharged on non-steroidal anti-inflammatories, two of 39 did not receive NSAIDs or prednisolone at any time point. The median duration of hospitalisation for those admitted was 5 days (range, 1 to 21 days). Where follow-up was available, relapse occurred in eight of 25 cases before reaching skeletal maturity. At the time of metaphyseal osteopathy diagnosis, five of 39 cases had concurrent conditions. Where follow-up was available, four of 25 developed future immune-mediated conditions. Metaphyseal osteopathy should be considered in non-ambulatory painful young dogs. Some dogs developed future immune-mediated conditions, which may support the hypothesis that metaphyseal osteopathy is an autoinflammatory bone disorder. Further studies with a larger cohort are required to determine the clinical significance of this.

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Determinants of Quality of Life in Adult Patients with Chronic Non-Bacterial Osteomyelitis (CNO) of the Sternocostoclavicular Region (SCCH): A Dutch Single Center Study.

Sternocostoclavicular hyperostosis (SCCH), the main clinical manifestation of chronic non-bacterial osteomyelitis (CNO) in adults, is associated with various degrees of chronic pain and restricted shoulder girdle function. We evaluated the impact of CNO/SCCH on quality of life (QoL) and its determinants in 136 adult patients with this rare auto-inflammatory bone disorder using the Short Form 36, Brief Pain Inventory, Brief Illness Perception, Utrecht Coping List, and Shoulder Rating questionnaires. Data were compared with those of the general Dutch population, patients with chronic pain, fibrous dysplasia, or osteoarthritis. Eighty-six (64%) predominantly female (85%) patients with completed questionnaires were included in the study. Sixty-four (75%) had isolated CNO/SCCH. Mean delay in diagnosis was 3.0 ± 5.5 (SD) years, 90% had variable pain, and 84% limited shoulder function. Compared to healthy and chronically diseased reference populations, CNO/SCCH patients demonstrated significant impairments in almost all aspects of QoL, maladaptive illness perceptions, and ineffective coping strategies. For patients with >5-year delay in diagnosis, higher pain scores and limited shoulder function were identified as determinants for impaired QoL. Patients with CNO/SCCH reported significant impairments in QoL associated with clinical and psychological determinants. Clinical measures such as shortening delay in diagnosis, effective pain management, and psychosocial interventions targeting these factors should help minimize the negative impact of CNO/SCCH on QoL.

O13 A case of chronic recurrent multifocal osteomyelitis

O13 A case of chronic recurrent multifocal osteomyelitis

Chronic Nonbacterial Osteomyelitis in Children

Chronic nonbacterial osteomyelitis (CNO) is an auto-inflammatory bone disorder with a wide spectrum of clinical manifestations, from unifocal to multifocal lesions. When it manifests with multifocal lesions, it is also referred to as chronic recurrent multifocal osteomyelitis (CRMO). CNO/CRMO can affect all age groups, with the pediatric population being the most common. Patients may present with systemic inflammation, but there is no pathognomonic laboratory finding. Magnetic resonance imaging (MRI) is the gold standard radiological tool for diagnosis. In the absence of validated diagnostic criteria, CNO/CRMO remains an exclusion diagnosis. Bone biopsy does not show a specific disease pattern, but it may be necessary in unifocal or atypical cases to differentiate it from malignancy or infection. First-line treatments are non-steroidal anti-inflammatory drugs (NSAIDs), while bisphosphonates or TNF-α blockers can be used in refractory cases. The disease course is unpredictable, and uncontrolled lesions can complicate with bone fractures and deformations, underlying the importance of long-term follow-up in these patients.

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 of the Sternocostoclavicular Region in Adults: A Single-Center Dutch Cohort Study.

ABSTRACTSternocostoclavicular hyperostosis (SCCH) is a rare autoinflammatory bone disorder caused by chronic nonbacterial osteomyelitis (CNO), which is associated with sclerosis and hyperostosis primarily affecting the sternum, the medial end of the clavicles, and the first ribs. Other areas of the axial skeleton may also be affected. The more severe synovitis–acne–pustulosis–hyperostosis–osteitis (SAPHO) syndrome is additionally associated with dermatoses and joint manifestations. This Dutch retrospective cross‐sectional single‐center cohort study characterizes the spectrum of clinical features in adult CNO/SCCH patients at the time of diagnosis. The only inclusion criteria was the availability of complete sets of clinical and imaging data systematically collected over three decades using in‐house protocols. Data from 213 predominantly female patients (88%) with a median age of 36 years at presentation were studied. The mean diagnostic delay was 5 ± 5 years. The main symptoms were chronic pain (92%), bony swelling (61%), and restricted shoulder girdle function (46%); 32% had palmoplantar pustulosis and 22% had autoimmune disease. The majority (73%) had isolated SCCH; 59 (27%) had additional localizations in vertebrae (19%), the mandible (9%), or both (2%); 4 had SAPHO. The prevalence of current or past smoking was high (58%), particularly for patients with palmoplantar pustulosis (76%). There was a significant relationship between delay in diagnosis and both the extent of affected skeletal sites (p = 0.036) and erythrocyte sedimentation rate levels (p = 0.023). Adult‐onset CNO is characterized by distinctive clinical and radiological features, but diverse aspects of its spectrum are currently not fully captured by a comprehensive classification. Delayed diagnosis is still common and potentially associated with irreversible structural changes and debilitating chronic symptoms, increasing the burden of illness and negatively impacting on quality of life. It is hoped that findings from this study will dispel confusion about nomenclature and classification of adult‐onset CNO and increase awareness of its distinctive clinical and radiological features, and thus facilitate early diagnosis and referral for treatment, which should positively impact prognosis by preventing disease progression, although this remains to be established. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.