Multifocal Osteomyelitis Research Articles

Not all benign: disease course, complications, and sequalae of chronic recurrent multifocal osteomyelitis in children.

Advances in pathogenesis of chronic recurrent multifocal osteomyelitis in children (CRMO) have shaped therapeutic strategies. The use of whole-body MRI (WBMRI) and improved awareness of CRMO has increased rates and timeliness of CRMO diagnoses. In this review, we highlight the findings from recently published CRMO cohorts and describe the course, complications, and long-term sequalae of CRMO. It is important for clinicians to be aware of the potential for long-term sequelae in order to optimize therapy and avoid complications. Despite recent advances in defining disease pathogenesis, children with CRMO continue to suffer from complications and deformities. Involvement of the spine can be asymptomatic and is not as rare as previously suggested. This can result in damaging outcomes, such as vertebral fractures and permanent deformities. A subset of patients has polycyclic disease course and some continue to have active disease for years and well into adulthood, with significant impacts on quality of life. These recent findings have considerable implication on clinical practice regarding diagnosis, treatment, and monitoring of the disease. Collectively, they support the need for continued monitoring of the disease and screening using comprehensive imaging, such as WBMRI.

Use of zoledronic acid in pelvic and sacral chronic recurrent multifocal osteomyelitis (CRMO): a case report

Alisi, Mohammed S. MDa,b; Hammad, Yazan MDa; Al-Ali, Hani MDc; Abu Hassan, Freih FRCS (Tr & Orth)a Author Information

Research priority setting for paediatric rheumatology in the UK.

The evidence base that underlies the management of children and young people with paediatric rheumatic diseases is deficient. In this field, there are many crucial unanswered questions. The UK Paediatric Rheumatology Clinical Studies Group, supported by UK National Institute for Health Research Clinical Research Network: children and Versus Arthritis, elicited ideas for research priorities from paediatric rheumatologists, trainees, allied health-care professionals, nurse specialists, patients, parents of patients, carers, and charities. These ideas were collected through online surveys and face-to-face meetings. A modified Delphi process was used, which included online research priority ranking surveys and a consensus workshop. A longlist of 55 disease-specific research priorities and 37 general research priorities were voted on in the first survey. A list of 11 top general research priorities was produced. The top ten disease-specific research priorities were discussed in depth at a Delphi workshop to determine their final ranking. This Health Policy paper will help to guide clinicians, academics, and funding bodies to prioritise research in paediatric rheumatic diseases, specifically in areas of unmet patient needs.

Whole-body MRI at initial presentation of pediatric chronic recurrent multifocal osteomyelitis and correlation with clinical assessment.

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. To retrospectively characterize distribution of disease on WB-MRI and to correlate imaging findings with disease severity at initial rheumatology presentation. 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. 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. 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.

Does SAPHO syndrome exist in dermatology?

In the late 1960s, palmoplantar pustulosis (PPP) with sternocostoclavicular arthropathy was first described in Japan, predominantly affecting women in the perimenopausal age. In the 1970s, the chronic non-bacterial osteomyelitis and chronic recurrent multifocal osteomyelitis were initially observed in paediatric patients with approximately 70% girls. Acne fulminans accompanied by polyarthralgia have been observed since early 1970s, which almost exclusively occurs in adolescent boys. Report on spondyloarthropathy associated with hidradenitis suppurativa can be traced back to 1982. The SAPHO syndrome was coined in 1987 to lump together synovitis, acne, pustulosis, hyperostosis and osteitis to conceptualize a group of inflammatory osteocutaneous diseases of unclear etiopathogenesis and ill-defined associations spanning disparate age and gender groups. From historical view, Sasaki syndrome is proposed to replace SAPHO syndrome to represent PPP with sternocostoclavicular arthropathy in the absence of other skin manifestations. Hidradenitis suppurativa is folliculitis in pathogenesis and no longer classified as acne. PPP accompanied by psoriasis vulgaris is more likely psoriasis pustulosa palmoplantaris in dermatological aspect, and the associated arthritis is part of psoriatic arthropathy. Pathophysiology of these disorders is incompletely understood. To echo the advancement of high-throughput sequencing, splitting but not lumping of clinical findings would be a better strategy to decipher these multigenic complex inflammatory disorders.

Pediatric Patients With a Dual Diagnosis of Inflammatory Bowel Disease and Chronic Recurrent Multifocal Osteomyelitis: A Single-Centre Case Series - Response to Letter to the Editor.

Pediatric Patients With a Dual Diagnosis of Inflammatory Bowel Disease and Chronic Recurrent Multifocal Osteomyelitis: A Single-Centre Case Series - Response to Letter to the Editor.

Effectiveness of pamidronate therapy in chronic recurrent multifocal osteomyelitis (CRMO) with thoracic/lumbal spine localization – a case report

Effectiveness of pamidronate therapy in chronic recurrent multifocal osteomyelitis (CRMO) with thoracic/lumbal spine localization – a case report

Missing Information Regarding Chronic Recurrent Multifocal Osteomyelitis and Inflammatory Bowel Disease.

Journal of Pediatric Gastroenterology and Nutrition: May 2022 - Volume 74 - Issue 5 - p e129 doi: 10.1097/MPG.0000000000003407

Transverse Myelitis in a Child with Chronic Recurrent Multifocal Osteomyelitis.

A 16-year-old girl with a history of clavicular chronic recurrent multifocal osteomyelitis (CRMO) presented with fever, vomiting, urinary and bowel retention, thigh paresthesia, and back pain for 2days. The patient had 2 separate viral illnesses within a month prior to presentation. Spine magnetic resonance imaging (MRI) displayed increased T2 hyperintensity of the central grey matter from C3 to the conus medullaris (Figure 1). Findings were consistent with longitudinally extensive transverse myelitis. Cerebrospinal fluid analysis revealed elevated protein (51; reference range: <48mg/dL), IgG index (.74; reference range <.70), and glucose (99; reference range 40-75mg/dL). There was pleocytosis of 22 white blood cells (88% lymphocytes and 12% monocytes) with negative AQP4 and MOG antibodies. COVID-19 spike protein was positive with a negative PCR and non-immunized status, suggesting prior infection. Four months later, a pelvic MRI revealed new evidence of CRMO.

OA32 UK Paediatric Rheumatology Clinical Studies Group research priorities - results of a multidisciplinary consultation and consensus exercise

Abstract Background/Aims The evidence base underlying the management of children and young people (CYP) with paediatric rheumatic diseases (PRDs) is inadequate, with many critical outstanding questions warranting investigation. The aim of this study was to elicit multidisciplinary PRDs research priorities, through consultation with patients, carers and healthcare professionals. Methods This study was led by the UK NIHR CRN Children/Versus Arthritis Paediatric Rheumatology CSG (referred to as ‘the CSG’) and its Topic Specific Groups (TSGs). The CSG is a multidisciplinary group with strong patient/parent representation, supporting the development of clinical studies in the UK. Research priority ideas were sought from paediatric rheumatologists, trainees, allied healthcare professional (AHP), nurses, patients, parents and charities, through online surveys and face-to-face meetings. Research ideas were categorised as disease-specific or broad/general. They were grouped into sub-themes, duplicates/questions that had already been answered were removed, and similar submissions combined. A modified Delphi process was undertaken, including online research priority ranking, and an online consensus workshop to derive top PRD research priorities. Results The initial consultation yielded 304 research priority ideas; 25% from patients/parents, 22% from the CSG, 18% from TSGs, 13% from AHPs, 11% from trainees, 11% from Nurses. 55 disease-specific and 37 broad/general research priorities were voted upon in the first online survey, yielding a top 11 general broad research priorities. The top 10 disease specific priorities were discussed at the online Delphi priority setting workshop, and two online surveys were held during the workshop to determine their final ranking. Two of the disease-specific priorities were combined, leading to a top 9 (see Table). Disease specific proprieties related to clinical trials in JIA (n = 3) / Juvenile Dermatomyositis (n = 1) / Chronic Recurrent Multifocal Osteomyelitis (n = 1) / Juvenile Systemic Lupus Erythematosus (n = 1) Scleroderma (n = 1), management of JIA in adulthood (n = 1) and chronic pain (n = 1). Conclusion UK consensus-based PRD research priorities have been derived, underpinned by collaboration with patients/carers and healthcare professionals, helping to guide funding bodies to improve the evidence base in PRD’s. Disclosure E.M.D. Smith: None. N. Egbivwie: None. K. Cowan: None. A.V. Ramanan: None. C.E. Pain: None.

Clinical and Genetic Features of Chinese Adult Patients With Chronic Non-Bacterial Osteomyelitis: A Single Center Report.

ObjectivesChronic non-bacterial osteomyelitis (CNO) is a rare polygenic autoinflammatory bone disease. We aimed to characterize the clinical manifestations and gene variants of Chinese adult patients with CNO.MethodsBy reviewing data of all CNO patients being diagnosed and followed up at the Center for Adult Autoinflammation Diseases, Department of Rheumatology, Peking Union Medical College Hospital, clinical and genetic features of these patients were evaluated and concluded.ResultsThe median age of disease onset was 19 (6-64) years old, and adult-onset was observed in 6 (60%) patients. The mean time of diagnosis delay was 92 ± 78 months. The common symptoms were bone pain (10, 100%), fever (9, 90%), and arthritis (6, 60%). In total, there were 54 skeletal lesions, and each patient had no less than 2 lesions. The most frequently affected sites included lower limbs (20.5%), mandible, vertebrae and pelvis (17.5%, separately). Variants of 4 genes were detected in our study including COL1A1, PSTPIP1, LRP5 and CLCN7. In seven patients who were treated with combination therapy containing tumor necrosis factor (TNF) α inhibitors, five (55.6%) had a complete response and 2 (44.4%) had a partial response.ConclusionThis is the first and largest case series of CNO in the Chinese adult patients. Four novel genetic mutations potentially associated with CNO were identified. Notably, CNO should be considered in the differential diagnosis of adult patients with long disease course and recurrent multifocal osteomyelitis of unknown cause, and these patients might benefit from combination therapy containing TNFα inhibitors.

A Pain in the Neck: An Adolescent with Neck Pain.

A Pain in the Neck: An Adolescent with Neck Pain.

Analysis of the fecal and oral microbiota in chronic recurrent multifocal osteomyelitis

BackgroundChronic 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.MethodsIn 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.ResultsNotably, 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.ConclusionsBacterial 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.

Colchicine as rescue treatment in two pediatric patients with chronic recurrent multifocal osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic autoinflammatory bone disease characterised by noninfective inflammation of bones. Diagnostic approach is challenging and requires exclusion of other causes such as malignancies or infections. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are usually applied as first-line therapy in CRMO patients; however, some cases require more intensive therapy with second-line agents to control disease activity. We hereby describe the use of colchicine as a nonconventional second-line disease-modifying antirheumatic drug in two pediatric patients with CRMO refractory to NSAIDs and corticosteroids. Our data indicate that colchicine might prove an important area for future research as a potential therapeutic option with easy administration, low cost, and a good safety profile in CRMO patients refractory to first-line therapy.

Chronic Recurrent Multifocal Osteomyelitis Associated With Inflammatory Bowel Disease Successfully Treated With Infliximab

Chronic Recurrent Multifocal Osteomyelitis Associated With Inflammatory Bowel Disease Successfully Treated With Infliximab

Chronic Recurrent Multifocal Osteomyelitis (CRMO): An Unusual Presentation of Limb Pain

Chronic recurrent multifocal osteomyelitis (CRMO), known as nonbacterial osteomyelitis, is an autoinflammatory disease with periodic exacerbations, also known as nonbacterial osteomyelitis. It is a rare, noninfectious inflammatory disorder characterized by multifocal bony lesions with pain. Conventional X-ray and CT imaging show multiple osteolytic and sclerotic lesions in the affected limbs. It is a great challenge for pediatricians to diagnose this disease for its rarity. Early diagnosis, regular follow-up and appropriate treatments are mandatory to reduce morbidity and prevent these disease complications. We report here two cases of CRMO who presented with pain, swelling and redness of multiple sites of lower limbs from the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). Clinical features, laboratory findings, and characteristic radiological findings were strongly suggestive of CRMO.

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.

Case of the Season: Asymmetric Chronic Recurrent Multifocal Osteomyelitis

Chronic recurrent multifocal osteomyelitis is a rare noninfectious inflammatory bone disease diagnosed based on the synthesis of clinical, radiological, and pathological findings. The differential diagnostic considerations are led by multifocal infectious osteomyelitis and multifocal neoplasms. We report a case of a 9-year-old girl who emergently presented with worsening back pain, inability to walk, and normal vital signs. C-reactive protein and erythrocyte sedimentation rate were elevated, whereas the white blood cell count was normal. Initial radiographs and MRI of the spine showed multiple edematous vertebral body lesions. Subsequent whole-body MRI demonstrated multiple additional edematous bone lesions in the right half of the body, including the scapula, femur, and tibia. The lack of symmetrical bone lesion distribution indicated image-guided percutaneous core biopsy to exclude neoplastic disease. Pathological examination of an osseous core biopsy specimen showed a noninfectious osteomyelitis pattern with no findings of Langerhans cell histiocytosis, malignancy, or infectious osteomyelitis. The synthesis of clinical, radiological, and pathological findings was diagnostic of asymmetric right-sided chronic recurrent multifocal osteomyelitis, representing an atypical presentation that deviates from the typically symmetrical bilateral chronic recurrent multifocal osteomyelitis pattern.

Early diagnosis and response assessment in chronic recurrent multifocal osteomyelitis: changes in lesion volume and signal intensity assessed by whole-body MRI

Objective:To assess the effectiveness of whole-body MRI (WB-MRI) in early diagnosis of chronic recurrent multifocal osteomyelitis (CRMO) and the prediction of clinical response through quantitative MRI features.Methods:20 children (mean age, 10.3 years; range, 5–14 years) with CRMO underwent WB-MRI and were assessed with a clinical score (Jansson) at baseline (median time after first encounter, 8 months) and follow-up (median time after baseline, 11.5 months). Baseline WB-MRI scans were classified as early (within 6 months after first encounter) and late. Clinical responders and non-responders were compared regarding number and localization of bone lesions, lesion volume and T2 signal intensity (SI) ratio (lesion to muscle).Results:Diagnosis of CRMO was made promptly in the early WB-MRI group (n = 10; median, 3 months) compared to the late WB-MRI group (n = 10; 18 months; p = 0.006). Bone lesions were mainly located in the lower extremities (n = 119/223; 53%). No significant difference was detected regarding the number of bone lesions and lesion volume in the subgroups of clinical responders (n = 10) and non-responders (n = 10). Responders showed a higher volume reduction of bone lesions at follow-up compared to non-responders (p = 0.03). Baseline and follow-up SI ratios were lower in responders (5.6 and 5.8 vs 6.1 and 7.2; p = 0.047 and p = 0.005).Conclusion:The use of WB-MRI within 6 months of disease suspicion may serve as a benchmark to support early diagnosis of CRMO. T2 SI ratios and the reduction of lesions’ volume correlate with clinical outcome.Advances in knowledge:WB-MRI at an early stage of suspected CRMO plays a key role for early diagnosis. This is the first study showing that quantitative MRI features are suitable for response assessment and can be used as prognostic markers for the prediction of clinical response.

Chronic recurrent multifocal osteomyelitis: A multidisciplinary experience of 22 pediatric cases with a mean follow-up of 27 months

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is not a well known disorder among nonpediatricians. The aim of this study is to retrospectively evaluate the clinical outcomes of twenty-two CRMO patients presenting to two referral centres. MethodsThis retrospective study included twenty-two children (12 males, 10 females; mean age 13 years; range 7–17 years). The diagnosis was based on clinical, radiological, and pathological findings. Data were retrieved from hospital charts. ResultsThe mean delay in diagnosis was 26 months (range, 0–96 months). The mean follow-up after diagnosis was 27.4 months (range, 6–47 months). Symptoms included pain, limping, local swelling, morning stiffness, and fever. 18 patients had multifocal and 4 patients had unifocal disease. Bone lesions were detected with whole-body or local MRI (Magnetic Resonance Imaging). The mean number of bone lesions was 2.5 (range, 1–8). Ten cases underwent biopsy to exclude malignancy and infection. Prior to diagnosis, cast immobilization or curettage was erroneously performed in four patients. One patient suffered from vertebral compression fracture. There is no growth disturbance or deformity in any patient. ConclusionThis study demonstrated that early recognition of the disease can be improved by using Bristol criteria which should be evaluated by a multidisciplinary team rather than one single specialist. In this way, the reliability of these criteria is improved and the treatment could be given earlier with decreased delay in diagnosis. This multidisciplinary approach is also important for decision for biopsy, timely aggressive medical treatment, and follow-up of the disease to minimise possible complications.