Recurrent Multifocal Osteomyelitis In Children 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.

Patient-reported effectiveness and safety of Pamidronate in NSAIDs-refractory chronic recurrent multifocal osteomyelitis in children

To evaluate patient-reported effectiveness, safety and social influence of Pamidronate in the therapy of NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis in children. Authors reviewed self-created questionnaires, which asked patients for symptoms alleviation, adverse drug reactions frequency and degree of severity and daily activities self-reliance. Only surveys with complete answers, which were returned to authors by an e-mail from juvenile patients treated for NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis at the University Children’s Hospital of Cracow were analyzed. Between 2010 and 2019, 61 children were diagnosed with NSAIDs-refractory Chronic Recurrent Multifocal Osteomyelitis at our department. Out of 61 requests sent, 42 complete replies (33 females, 9 males) were gathered and analyzed. All patients included in this research were administered with at least one set of Pamidronate intravenously in the dose of 1 mg/kg/day for 3 consecutive days. Our analysis shows remarkable in terms of patient’s impressions decrease of pain intensity after 2.5 series of Pamidronate on average, and total pain resolution after 5.9 series on average. Overall number of adverse drug reaction events reported by responders was 105. One patient developed drug-dependent renal insufficiency in the course of therapy. Outcome assessment indicates that nearly 50% of the studied population was more eager to participate in social life just after the first infusion of the drug. 95% of the surveyed unanimously agreed to recommend Pamidronate therapy to cure NSAIDs-refractory CRMO. 39 out of 42 (93%) patients considered Pamidronate effective at the end of the treatment. Onset of Pamidronate’s action is gradual and differs in terms of symptoms alleviation between sexes. The therapy can induce considerable number of adverse drug reactions (2.5 per patient). Only 3 out of 42 (7%) patients were free from any ADRs. To demonstrate the impact of the use of Pamidronate on daily activities more precisely, further research with quantification of the quality of life is warranted.

Chronic recurrent multifocal osteomyelitis in children with hypophosphatasia explained by anti-inflammatory nucleotidase activity of tissue nonspecific alkaline phosphatase in mesenchymal and hematopoietic cells

Chronic recurrent multifocal osteomyelitis in children with hypophosphatasia explained by anti-inflammatory nucleotidase activity of tissue nonspecific alkaline phosphatase in mesenchymal and hematopoietic cells

Chronic recurrent multifocal osteomyelitis in children: a single center experience over five years.

Sağ E, Sönmez HE, Demir S, Bilginer Y, Ergen FB, Aydıngöz Ü, Özen S. Chronic recurrent multifocal osteomyelitis in children: a single center experience over five years. Turk J Pediatr 2019; 61: 386-391. Chronic recurrent multifocal osteomyelitis (CRMO) is a rare disease characterized by sterile bone inflammation. It is an orphan disease with many unclear aspects in terms of diagnosis, treatment and follow-up. The aim of this study was to report our experience of pediatric CRMO patients. Children who were diagnosed with CRMO, and were followed-up between January 2008 and January 2017, were included in this study. There were 15 CRMO patients (8M/7F) with a median age at diagnosis of 9.0 years (range: 0.6-15.0). Bone pain was the most common presenting symptom. All of the patients had multifocal bone lesions. Vertebrae (66.7%) and femur (66.7%) were the most commonly affected bones. Eight of the patients also had sacroiliitis; however, only one of them was HLA-B27 positive. Whole-body magnetic resonance imaging (MRI) was used as a diagnostic tool in 13 patients revealing bone marrow edema (84.6%), osteitis (69.2%), and periosteal reaction (61.5%). All patients were initially treated with non-steroidal anti-inflammatory drugs (NSAIDs), however, disease-modifying anti-rheumatic drugs, anti-TNF agents or pamidronate were added to therapy due to inadequate treatment response. Clinical remission was achieved in 12 patients (1 with NSAIDs, 3 with methotrexate, 1 with pamidronate and 7 with an anti-TNF agent). During the follow-up period, relapses were observed in four patients who presented with pain and/or a newly formed bone lesion on MRI. Eventually, however, all of these patients also reached remission. CRMO is a chronic disease which may have a progressive or relapsing-remitting course. Improvement of the knowledge about this rare disease may help to enlighten the unknowns of the disease.

Recurrent Multifocal Osteomyelitis in Children: Experience in a Tertiary Care Center

IntroductionChronic recurrent multifocal osteomyelitis is a rare aseptic bone inflammation that affects paediatric patients. Its management and treatment have not yet been standardised. MethodsRetrospective, descriptive study of patients under 14 years of age diagnosed with chronic nonbacterial osteomyelitis (CNBO) in a tertiary hospital. We included patients diagnosed over the last 6 years (2010–2015) who met the Jansson criteria. The clinical and radiological characteristics of CNBO were analysed, as was the outcome after different therapeutic options. ResultsWe report 12 patients, with a mean age of 11 years (±1.6 standard deviation [SD]) and female predominance (10:2). The mean number of foci was 3.5 (±2.2 SD). The most common locations were ankle (58%), clavicle (50%), sternum (33%) and hip (25%). The mean disease duration was 10.5 months (±10.3 SD), and the median time to diagnosis was 2.38 months (range 0.17–16). Bone scintigraphy detected asymptomatic foci in 33% and we detected lytic lesions in 50% through magnetic resonance imaging. Biopsy was performed in 60%; 2/12 (16%) were associated with inflammatory disease and 1/12 (8.3%) later developed lymphoma. In all, 58% received antibiotic therapy with little response, 100% anti-inflammatory agents, 50% systemic corticosteroids, 41.6% methotrexate/pamidronate and 16% anti-tumour necrosis factor (TNF) α. The mean duration of treatment was 14.8 months (±12.4 SD) and 66% had recurrences. Currently, 83% are in clinical remission without treatment. ConclusionsWhen CNBO is refractory to treatment with anti-inflammatory drugs, intravenous pamidronate can be an alternative. Anti-TNF drugs can be considered in patients who fail with pamidronate, as can agents associated with other autoimmune conditions.

Chronic recurrent multifocal osteomyelitis in children affected by inflammatory bowel disease

Chronic recurrent multifocal osteomyelitis in children affected by inflammatory bowel disease

An Update on the Pathogenesis and Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children.

Chronic recurrent multifocal osteomyelitis (CRMO), also known as chronic non-bacterial osteomyelitis (CNO), is a rare inflammatory disorder that primarily affects children. It is characterized by pain, local bone expansion, and radiological findings suggestive of osteomyelitis, usually at multiple sites. CRMO predominantly affects the metaphyses of long bones, but involvement of the clavicle or mandible are suggestive of the diagnosis. CRMO is a diagnosis of exclusion, and its pathogenesis remains unknown. Differential diagnosis includes infection, malignancies, benign bone tumors, metabolic disorders, and other autoinflammatory disorders. Biopsy of the bone lesion is not often required but could be necessary in unclear cases, especially for differentiation from bone neoplasia. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment. Alternative therapies have been used, including corticosteroids, methotrexate, bisphosphonates, and tumor necrosis factor (TNF)-α inhibitors. No guidelines have been established regarding diagnosis and treatment options. This manuscript gives an overview of the most recent findings on the pathogenesis of CRMO and clinical approaches for patients with the condition.

Chronic recurrent multifocal osteomyelitis in children and adults: current understanding and areas for development.

Since the first descriptions of chronic recurrent multifocal osteomyelitis in the 1970s, there have been numerous case reports in the literature; both unusual case reports and case series from all over the world. Our understanding of the pathogenesis has significantly changed, with it now being regarded as an autoinflammatory condition. Treatment options have also expanded, but little progress has been made in developing the evidence for treatments. Advancing gene studies have provided a mouse model, but the quest for a single gene to match the phenotype has been elusive. Early cohorts of patients have grown up into adults, allowing prospective data to inform the expected outcomes.

Chronic recurrent multifocal osteomyelitis in children: a new, MRI-based method of quantifying inflammation in the bone

Chronic recurrent multifocal osteomyelitis in children: a new, MRI-based method of quantifying inflammation in the bone

Chronic recurrent multifocal osteomyelitis in children: nine years' experience at a statewide tertiary paediatric rheumatology referral centre.

To describe the clinical features, management and outcome of 34 children with chronic recurrent multifocal osteomyelitis (CRMO) diagnosed at a single centre over 9 years. All children identified with CRMO for the period 2005-13 were identified from a prospectively collected database, with additional data from hospital records. Thirty-four patients, 21 female and 13 male, were identified. The average age at symptom onset was 9.8 years (range 3.8-17.9) and at diagnosis was 10.9 years (range 5.2-18.2), with an average delay in diagnosis of 12 months. Follow-up was 0.3-7.9 years (average 2.1), with 104 individual bony lesions identified, with a median of 3 (range 1-9) per patient. Six patients had unifocal disease. The sites involved included the tibia (n = 19), femur (n = 14), clavicle (n = 12), vertebrae (n = 10) and fibula (n = 8). Approximately half of patients had an inflammatory arthritis at diagnosis, and two-thirds in total eventually developed an arthritis. Pustulosis occurred in eight patients (24%), severe acne in four (12%) and psoriasis in three (9%). NSAIDs were used in 91%, CSs in 82% and MTX in 38%. Two patients were treated with anti-TNF agents. Episodic disease was most common (79%), while 21% had a monophasic pattern. Clinical remission occurred in 94% of children, with prolonged remission in 17%. Seven patients did not require medications for >12 months. CRMO is more common than previously recognized, but diagnosis may be delayed. Episodic multifocal disease was most common, but some had unifocal and/or monophasic disease. Most patients responded to NSAIDs and/or intermittent CSs, but many required DMARDs.

Conservative Treatment of Chronic Recurrent Multifocal Osteomyelitis in Children

The experience in diagnosis (52 patients) and treatment (35 patients) of chronic recurrent multifocal osteomyelitis in children is presented. In 17 patients conservative treatment was accompanied by surgical intervention. Eighteen patients received the conservative treatment only. Analysis covering medical documentation and authors observation showed that antibacterial therapy that was performed both before hospitalization of patients to CITO (20 patients) and at the institute (21 patients) was ineffective. Original scheme of conservative treatment with application of hormonal, nonsteroid antiinflammatory and metabolic therapy is given. Long term complex therapy proved sufficiently high efficacy of that treatment method and allowed to overcome the pessimism in prognosis of that disease.

Chronic recurrent multifocal osteomyelitis in children

Chronic recurrent multifocal osteomyelitis in children

Chronic recurrent multifocal osteomyelitis in children

Thirty cases of chronic recurrent multifocal osteomyelitis have been reported in the literature. A radiologic evaluation of thirty-one additional cases, 25 of whom also underwent bone scintigraphy, is presented. Bone biopsy specimens were obtained in 16 patients. Most lesions were located in the metaphyses of the long bones adjacent to the physis and had a characteristic, probably pathognomonic appearance. Extension into the epiphyses was rare. Lesions in the vertebral bodies, clavicle and pelvis had possibly a less specific radiographic appearance. Lesions in short tubular bones were non-specific. Bone scintigraphy had a practical value in evaluating the global distribution of lesions including asymptomatic lesions and lesions in the spine or pelvis, the latter being somewhat hard to detect with conventional radiography. All biopsies showed acute, subacute or chronic unspecific osteomyelitis, sometimes mixed in the same lesion. Staining for bacteria and fungi was negative.

Pustulosis palmaris et plantaris: Its association with chronic recurrent multifocal osteomyelitis

Palmoplanar pustules may rarely be associated with chronic recurrent multifocal osteomyelitis in children and young adults, Additional features of this disorder are recurrent low-grade fevers and bone pain. Skeletal radiographs and bone films suggest osteomyelitis, but bone cultures yield no growth of organisms. The cause of this disorder is unknown, and treatment remains unsatisfactory.