Chronic Recurrent Multifocal Osteomyelitis Research Articles

The multi-kinase inhibitor dasatinib suppresses autoinflammation and increases bone density in a mouse model for chronic recurrent multifocal osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease that presents with bone destruction and pain. Although genetic studies have identified signalling pathways involving CRMO, molecularly targeted drugs remain unavailable. We used an animal model of CRMO as an in vivo screening system for candidate therapeutic agents. A gain-of-function mutation in Fgr, a member of Src family kinases (SFKs), causes peripheral paw inflammation and reduced bone mineral density (BMD) in Ali18 mice. The SFK inhibitor dasatinib was selected for administration to Ali18 mice daily for 2 weeks. Local inflammation and BMD were assessed by clinical scoring and computed tomography, respectively. Pilot studies in a small number of animals showed that dasatinib administration effectively suppressed the early phase of autoinflammation in Ali18 mice. Serial oral gavage of dasatinib to a group of Ali18 mice confirmed significant suppression of paw swelling with no side effects. Histological analysis revealed that abnormal proliferative bone marrow cells and inflammatory infiltration into the skin in the affected area were clearly reduced in the animals with dasatinib administration. Further, trabecular BMD in Ali18 long bones was restored to levels similar to that found in wild type mice. Our results indicate that autoinflammation and related-bone phenotypes were completely suppressed by the dasatinib kinase inhibitor in CRMO model animals. Thus, it is strongly suggested that dasatinib can be used for clinical treatments of CRMO with the combination of molecular diagnosis of the FGR locus. SIGNIFICANCE OF THE STUDY: Autoinflammation and related-bone phenotypes were effectively suppressed by the kinase inhibitor dasatinib in CRMO model animals. In combination with molecular analysis of the FGR locus, dasatinib is a strong candidate for the clinical treatments of CRMO. We propose that the animal model employed in this study can be used to screen this and other potential drugs for CRMO.

Conventional Radiography and Ultrasound Imaging of Rheumatic Diseases Affecting the Pediatric Population

Juvenile idiopathic arthritis is the most frequent rheumatic disease in the pediatric population, followed by systemic lupus erythematosus, juvenile scleroderma syndromes, juvenile dermatomyositis, chronic recurrent multifocal osteomyelitis, and juvenile vasculopathies. The imaging approach to inflammatory connective tissue diseases in childhood has not changed dramatically over the last decade, with radiographs still the leading method for bony pathology assessment, disease monitoring, and evaluation of growth disturbances. Ultrasonography is commonly used for early detection of alterations within the intra- and periarticular soft tissues, assessing their advancement and also disease monitoring. It offers several advantages in young patients including nonionizing radiation exposure, short examination time, and high resolution, allowing a detailed evaluation of the musculoskeletal system for the features of arthritis, tenosynovitis, enthesitis, bursitis, myositis, as well as pathologies of the skin, subdermis, vessels, and fasciae. In this pictorial essay we discuss radiographic and ultrasound inflammatory features of autoimmune pediatric inflammatory arthropathies: juvenile idiopathic arthritis, lupus erythematosus, juvenile scleroderma, juvenile dermatomyositis and polymyositis.

MR Imaging of Rheumatic Diseases Affecting the Pediatric Population.

This article reviews the application of magnetic resonance imaging (MRI) to pediatric rheumatic diseases. MRI can detect early manifestations of arthritis, evaluate the extent of disease, and monitor disease activity and response to treatment.Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disorder, representing a diverse group of related diseases that share a definition of joint inflammation of unknown origin with onset before 16 years of age and lasting > 6 weeks. JIA may lead to significant functional impairment and is increasingly imaged with MRI to assess for active inflammation as a target for therapy. This is particularly true for juvenile spondyloarthritis that includes multiple subgroups of JIA and primarily involves the spine and sacroiliac joints.Other less common pediatric rheumatic diseases considered here are chronic recurrent multifocal osteomyelitis and collagen vascular diseases including polymyositis, dermatomyositis, scleroderma, and juvenile systemic lupus erythematosus.

Chronic nonbacterial osteomyelitis: description of three pediatric cases.

Chronic recurrent multifocal osteomyelitis (CRMO) or also called chronic non-bacterial osteomyelitis (CNO) is the most common autoinflammatory bone disease. It is characterized by the presence of symptomatic and non-symptomatic bone lesions, mono or multifocal. The main sites involved are the metaphyses of the long bones, the bones of the pelvis, the vertebrae, the clavicle, the mandible. Local symptoms include pain, swelling, and warmth in the absence or presence of fever. The inflammatory process can involve the skin (palmoplantar pustulosis or acne) and the intestine. Diagnosis is complex and uses imaging techniques (X-ray, total-body MRI, scintigraphy) as well as common laboratory tests aimed at identifying an inflammatory state. In doubtful cases, especially in the monofocal forms, it is mandatory to perform a biopsy examination to rule out malignancy. The differential diagnosis includes neoplastic diseases, chronic infections, metabolic diseases, traumatic outcomes. Treatment is not standardized and involves the use of non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, sulfasalazine, methotrexate, TNF inhibitors and bisphosphonates based on the experience of the individual centers. We report the experience of our Center (Operative Unit of Pediatrics S. Anna Hospital in Ferrara) with the description of 3 clinical cases, diagnosed from 2016 to 2018, treated with bisphosphonates with good clinical response and remission in two of them, while one patient had an adverse reaction to pamidronate and was subsequently successfully treated with methotrexate.

Diffuse large B-cell lymphoma in and of the bone. Forms and potential precursors

Primary diffuse large B-cell lymphoma of the bone (PB-DLBCL) is a rare event and is a diagnosis by exclusion of secondary bone involvement. Here we review the literature regarding PB-DLBCL and give essentials for this diagnosis. Furthermore, we give an overview of potential precursors and discuss chronic recurrent multifocal osteomyelitis (CRMO) as a potential risk factor for PB-DLBCL development in the young.

Assessing Knowledge and Promoting Awareness of Chronic Recurrent Multifocal Osteomyelitis Among Oral and Maxillofacial Surgeons

Chronic recurrent multifocal osteomyelitis (CRMO) is underdiagnosed and underreported because of a lack of awareness among providers. While patients with undiagnosed CRMO often present to oral and maxillofacial surgeons (OMSs) with a chief complaint of mandibular pain, to our knowledge, there is no literature regarding how well informed these providers are about this disease. Survey studies and educational efforts have been carried out among other specialists with the aim of raising awareness. The purpose of this study was to document current levels of understanding and determine knowledge gaps among OMSs regarding the diagnostic process for CRMO. For this cross-sectional cohort study, the investigators sent an anonymous and electronic survey to OMSs practicing in the United States. Using a clinical vignette, the survey captured respondents' ability to evaluate, diagnosis, and take appropriate next steps for a hypothetical patient with CRMO. A total of 429 respondents completed the entire survey. The following proportion of respondents correctly answered questions pertaining to information gathering (10.3%), differential diagnosis (9.8%), overall diagnostic workup (76.7%), diagnostic imaging (78.8%), diagnostic laboratory tests (36.8%), biopsy and specimen (0.5%), and final diagnosis and next steps (9.6%). Our findings demonstrate incomplete understanding of this disorder among OMSs and uncover knowledge deficiencies that can lead to misdiagnosis and/or delay in appropriate treatment. To improve patient outcomes, it is paramount to augment educational initiatives among practitioners regarding this disease.

Whole-body magnetic resonance imaging in inflammatory diseases: Where are we now? Results of an International Survey by the European Society of Musculoskeletal Radiology

PurposeTo investigate the current role of WB-MRI for rheumatic inflammatory diseases in clinical practice using a survey addressed to musculoskeletal radiologists. MethodsA survey composed of 61 questions, subdivided in three sections, demographics (five questions), application of WB-MRI for inflammatory musculoskeletal diseases in adults and children (28 questions: 7 open and 21 multiple choice for each subgroup) was distributed via the European Society of Musculoskeletal Radiology (ESSR) from July 2 to December 31, 2018 to radiologists working in academic, private, and public workplaces. Comparisons among the different workplaces were performed using the Chi-squared and the Kruskal-Wallis test for nominal and ordinal data, respectively (p < 0.05). ResultsSeventy-two participants out of the 1779 (4%) members of the ESSR with 10.4 ± 7.9 years of experience in musculoskeletal imaging, replied to at least one question. 30.6% and 12.3% of the respondents performed at least 50 WB-MRI examinations per year in adults and children, respectively. The most frequent indications were myositis in adults and chronic recurrent multifocal osteomyelitis (CRMO) in children, the latter mostly in academic centers (p = 0.013). The ESSR Arthrits Subcommitte's protocol was applied by half of the participants and especially radiologists working in private practice used it for adults (p = 0.025). Contrast medium was rarely used for adults particularly by academics (p = 0.04). Diffusion Weighted Imaging was applied for children mostly in private practice (p = 0.01) although, overall, it plays a marginal role. Scoring systems were rarely used. Ongoing research is limited. ConclusionWB-MRI is not routinely applied for musculoskeletal inflammatory diseases. The most frequent indications are myositis and CRMO.

Chronic recurrent multifocal osteomyelitis in a 3.5-year-old boy

We report an extremely rare case of multifocal bone disorder in a 3.5-year-old boy who appeared for left forearm and arm pain and multiple periods of fever with an unusual presentation of lymphoma/leukemia and highlight diagnostic challenges leading to a misdiagnosis, which was then diagnosed and treated for chronic recurrent multifocal osteomyelitis (CRMO). Based on a left arm biopsy and whole-body scans, he was eventually diagnosed with CRMO. Taken together, in this case, we noticed a notable amelioration after a 5-month treatment with nonsteroidal anti-inflammatory drugs on multiple bone pains.

Role of Physical Therapy and Rehabilitation in SAPHO Syndrome- A Rare Condition

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis) is heterogenous, rare entity with manifestations of Pustulo-Psoriatic Hyperostotic Spondyloarthritis (PPHS) and Chronic Recurrent Multifocal Osteomyelitis (CRMO). It can occur in all the age groups with unknown etiology. Hereby, author presents a case of 37-year-old female who reported with the complaint of bilateral knee pain and lower back pain. Laboratory investigations revealed elevated Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) levels. Bone scintigraphy and Magnetic Resonance Imaging (MRI) showed bone lesions, The diagnosis of SAPHO syndrome was made. The present article highlights the role of physical therapy as a non-pharmacological treatment modality to reduce pain, the intensity of which was measured by Numeric Pain Rating Scale (NPRS). The Range Of Motion (ROM) was measured by digital inclinometer and her Quality of Life (QoL) was measured by the 36-item short form health survey (SF-36) scale. Eight weeks postprotocol showed significant improvement in pain, ROM and QOL. This suggests a positive outcome of rehabilitation in SAPHO syndrome.

Pathophysiology and MRI Findings of Infectious Spondylitis and the Differential Diagnosis

MRI에서 추간판의 이상 신호와 위, 아래 척추체 종판의 파괴, 종판 주변의 골수부종 등은 감염성 척추염의 전형적인 소견으로 여겨지나 퇴행성 척추질환, acute Schmorl's node, 척추관절병증, synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)/chronic recurrent multifocal osteomyelitis, 척추신경관절병증, calcium pyrophosphate dehydrate 결절침착질환 등 다양한 비감염성 척추질환에서도 나타날 수 있다. MRI에서 이러한 비감염성 척추질환과 감별되는 감염성 척추염의 영상 소견은 추간판의 고신호와 농양, 척추 연부조직의 농양, 그리고 T1 강조영상에서 저신호로 보이는 종판의 경계가 불명확해지는 점 등이다. 그러나 이러한 감별점이 항상 적용되는 것은 아니며 감염성, 비감염성 질환의 영상 소견에 유사점이 많기 때문에 정확한 진단을 위해서는 감염성 척추염뿐만 아니라 감염과 감별해야 하는 다양한 질환의 병태생리와 연관된 영상학적 특징을 아는 것이 중요하다.

1369. The Spectrum of Chronic Osteomyelitis in Children

BackgroundWhile the majority of pediatric osteomyelitis cases are acute in nature, a significant subset present with prolonged symptoms often associated with substantial morbidity. Little data exist to guide clinicians in the management of these infections. We sought to describe the epidemiology, clinical features and management of chronic osteomyelitis in children.MethodsWe reviewed hospital admissions with an ICD10 code for chronic osteomyelitis from 2011-2018 at Texas Children’s Hospital. Cases were included if symptoms lasted >28 days on presentation. Patients diagnosed with chronic recurrent multifocal osteomyelitis were excluded. Cases were classified as those 1) associated with a contiguous focus (CoF), 2) penetrating or open trauma, 3) orthopedic hardware (OH), 4) post-acute chronic osteomyelitis (PACO, those occurring after >28 days of therapy for acute osteomyelitis) and 5) primary hematogenous chronic osteomyelitis (PHCO, those with 28 days of symptoms without other clear risk factors).Results114 cases met inclusion criteria. The median patient age is 11.8 years and 35.9% patients had underlying comorbidities. 83% of patients underwent a surgical procedure. Cases were diverse in terms of pathogenesis (Figure 1). A microbiologic etiology was identified in 72.8% of cases and was polymicrobial in 20.2% of cases; Staphylococcus aureus was the single most common etiology (Figure 2). CoF infection was more often associated with polymicrobial etiology with or without Pseudomonas (P< 0.001) and disease of the foot. PACO was caused by S. aureus in 95% of cases (p< 0.001, Figure 3). The overall median duration of total therapy was 210 days. 41% were discharged from hospital on OPAT with or without later transition to oral antibiotics. 26.3% of patients had persistent functional limitations at time of last follow-up of which 46% experienced repeat hospital admission/surgery. There was no association between duration of intravenous therapy and persistent functional limitations.Figure 1. Categories of Chronic Osteomyelitis Figure 2. Microbiology of Pediatric Chronic Osteomyelitis Figure 3. Clinical Features of Pediatric Chronic Osteomyelitis ConclusionChildren with chronic osteomyelitis are diverse both in terms of pathogenesis and microbiology. Pathogenesis and clinical presentation can provide clues to microbiologic etiology. Prolonged intravenous therapy does not appear to improve functional outcomes in chronic osteomyelitisDisclosures Jonathon C. McNeil, MD, Allergan (Research Grant or Support, Allergan provided ceftaroline powder for use in studies described in this abstract)

Crohn's disease and chronic recurrent multifocal osteomyelitis in a Japanese boy.

The authors declare no conflict of interest.

Chronic multifocal osteomyelitis: A case report and literature review

A case of chronic multifocal osteomyelitis was described in terms of its clinical manifestations, serological and imaging examinations, diagnostic criteria, treatment options, and follow-up evaluation after discharge. The pathogenesis, diagnosis, differential diagnosis and treatment of chronic multifocal osteomyelitis were reviewed, and the characteristics of autoinflammatory osteopathy were reviewed. The patient with onset from youth had developed severe skin lesions, progressive arthralgia and rachialgia. The clinical manifestation and the auxiliary examination of the patient accorded with the diagnosis of chronic multifocal osteomyelitis. After poor anti-inflammatory and analgesic effects, the switch to tumor necrosis factor alpha (TNF-α) inhibitor resulted in pain relief, normalization of inflammation indexes, and significant improvement in rash and imaging examination. Chronic recurrent multifocal osteomyelitis was a kind of autoinflammatory bone disease of multiple genes in disease with low incidence, unknown mechanism and unified diagnostic criteria. It was also known as chronic nonbacterial osteomyelitis, which was a rare, noninfectious inflammatory disorder that caused multifocallytic bone lesions characterized by periodic exacerbations and remissions. The exact pathophysiology or mechanism of the sterile bone inflammation was poorly understood, although chronic nonbacterial osteomyelitis was probably an osteoclast-mediated disease. In addition, an imbalance between pro- and anti-inflammatory cytokines was suspected to play a role. The available data so far pointed to the interplay among genetics, environmental, and immunologic factors as the causes of chronic nonbacterial osteomyelitis. Infectious etiology did not seem to play a crucial role in the pathogenesis of chronic nonbacterial osteomyelitis. It was often confused with metabolic bone disease, infection, tumor and other diseases. Its clinical manifestations were bone pain, fever, rash, fracture and so on. Laboratory examination showed significant increase in inflammatory markers. Radiographic examination revealed osteolytic or sclerosing changes. Magnetic resonance imaging was very useful for identifying bone lesions and tissue edema and was more accurate than bone emission computed tomography (ECT). Most of the patients begin to use non-steroidal anti-inflammatory drugs (NSAIDs) for treatment, but they are prone to relapse and new lesions appear. Other treatment options can be selected, including glucocorticoids, TNF-α inhibitors, bisphosphonates, methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs). Early diagnosis and treatment can prevent and reduce complications and improve prognosis.

Imaging of Joints and Bones in Autoinflammation.

Autoinflammatory disorders are commonly characterized by seemingly unprovoked systemic inflammation mainly driven by cells and cytokines of the innate immune system. In many disorders on this spectrum, joint and bone involvement may be observed and imaging of these manifestations can provide essential diagnostic information. This review aimed to provide a comprehensive overview of the imaging characteristics for major diseases and disease groups on the autoinflammatory spectrum, including familial Mediterranean fever (FMF), Behçet disease (BD), crystal deposition diseases (including gout), adult-onset Still’s disease (AoSD), and syndromatic synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)/chronic recurrent multifocal osteomyelitis (CRMO). Herein, we discuss common and distinguishing imaging characteristics, phenotypical overlaps with related diseases, and promising fields of future research.

Chronic recurrent multifocal osteomyelitis: diagnosis and treatment.

The aim of this article is to review recent findings regarding the diagnosis and treatment of chronic recurrent multifocal osteomyelitis (CRMO). An adequate understanding of pathophysiology along with the new advances in MRI imaging make it possible to determine the extent of disease and establish early treatment. TNF-α inhibitors and bisphosphonates have shown to be a well-tolerated and efficient treatment for CRMO providing both symptomatic relief and normalization of bone morphology. The results of recent studies suggest that a better knowledge of the genetic and molecular factors will allow early diagnosis and the development of more effective individualized treatments in the future.

Chronic Recurrent Multifocal Osteomyelitis in Children: A Single Center Experience

O bjective – To evaluate the suitability of diagnosing chronic recurrent multifocal osteomyelitis (CRMO) according to the Bristol diagnostic criteria and the clinical outcome of the children included in the study. M aterials and Methods – Retrospective- prospective study was conducted at the Clinic for Children’s Diseases, University Clinical Center Tuzla in the period from January 2018 to January 2020. The medical records of children treated CRMO were analyzed. R esults – Eight children fulfilled the Bristol diagnostic criteria. The median age at disease onset was 10.7 years. All children had multifocal lesions which relapsed in 2 chil- dren, and predominantly affected regions were the pelvis, hips, femur, spine and shoulder girdle. Hematological and biochemical parameters were unremarkable, although ESR was elevated in 6/8 children; all children had CRP<30 mg/L. For 3 children le- sions on plain radiography were observed; 49 lesions were verified on MRI (4 children had whole body MRI). Bone biopsy was performed in 2 children and it showed inflammatory changes. In 6/8 children treatment with NSAIDs was sufficient to control the disease during the 8-month period. However, two children had pain resistant to NSAID therapy, so they were treated with methotrexate and sulfasalazine. The child who received sulfasalazine treatment relapsed, so TNFα inhibitor (adalimumab) was used to control disease activity. No child received pamidronate. Conclusions – Our results showed that the use of the Bristol diagnostic criteria may obviate the need for a biopsy, shorten the time of diagnosis, save the bone from destruction, and avoid unnecessary treatments.

Bone involvement in Gaucher disease type 1: a differential diagnosis of multiple fractures in a young patient. Case report

Gaucher disease type 1 (GD1) is a rare inherited disease caused by mutations in the GBA1 gene, which encodes the lysosomal enzyme glucocerebrosidase, leading to decreased enzyme activity and the consequential accumulation of its substrate, glucosylceramide, within macrophages. Bone involvement in GD1 may include avascular necrosis, bone infarcts, fragility fractures, lytic or sclerotic bone lesions and osteomyelitis. Bone pain can manifest as an acute and very painful bone crisis or a chronic pain that might vary in intensity, usually caused by fractures or avascular necrosis with progressive collapse of bone and joints. Hence, this report aims to describe a case of Gaucher disease type 1 and discuss its diagnosis, bone involvement and management, since late diagnosis or inadequate therapy can lead to clinical worsening, irreversible mobility impairment and increased morbidity. AGR, a 32-year-old male patient, was admitted to the Rheumatology Service with a previous history of diffuse bone pain, episodic hyperemia in the lower limbs since the age of 9 and two low-impact fractures. He had an initial non-confirmed diagnostic hypothesis of chronic recurrent multifocal osteomyelitis and was taking dipyrone and tramadol to reduce pain. His physical examination evinced overweight (body mass index: 29.7 kg/m2) and hepatosplenomegaly. Laboratory tests shown thrombocytopenia, with platelet count 103,000/mm3 (reference value [RV]: 140,000-450,000/mm3), serum phosphorus 4.7 mg/dL (RV: 2.7-4.5 mg/dL), C-reactive protein 88.8 mg/dL (RV: &lt; 5 mg/dL) and ferritin 1336 ng/mL (RV: 30-400 ng/mL). Biochemical and bone turnover markers were normal, including serum total calcium and magnesium, parathyroid hormone, 25-OH vitamin D, alkaline phosphatase, procollagen type-I N-terminal propeptide and C-terminal telopeptide of type I collagen. Conventional radiographies and magnetic resonance imaging were performed and confirmed previous fractures in the right humerus and the right acetabulum. They also showed sclerotic lesions in the left femur and Erlenmeyer flask deformities in the distal femurs and the proximal tibias. Bone scintigraphy indicated a bone infarct area in the left tibia. Areal bone mineral density (BMD) evaluated by bone densitometry showed a left total femur Z-score of +4.3 and left femoral neck Z-score of +4.5. Differently, the bone microarchitecture and volumetric BMD, evaluated by a high-resolution peripheral quantitative computed tomography (HR-pQCT) at distal radius and distal tibia, demonstrated an impairment of cortical compartment with lower cortical thickness and lower cortical volumetric BMD, possibly contributing to the low-impact fractures. Considering the compatible radiological findings, associated with hepatosplenomegaly and thrombocytopenia, Gaucher disease type 1 became the major hypothesis. It was confirmed after enzymatic dosage, which showed low residual glucocerebrosidase activity and high serum chitotriosidase. Enzyme replacement therapy was started with taliglucerase alfa, a recombinant enzyme preparation that aims to supply the lacking glucocerebrosidase in lysosomes. After 6 months of treatment, patient reported a significant improvement in bone pain and general quality of life. Therefore, clinicians should be alert to young patients with multiple low-impact fractures and further evaluate other possible bone involvement, as GD1 may be a differential diagnosis. Since it needs specific treatment, early diagnosis can be crucial to avoid permanent bone damage and morbidity.

Chronic Recurrent Multifocal Osteomyelitis in Pediatric Crohn Disease, A Paradoxical Effect to Antitumor Necrosis Factor Alpha

Tumor necrosis factor-α (TNF-α) inhibitors have resulted in significant progress in the treatment of chronic inflammatory diseases. However, these therapies can lead to paradoxical immune-mediated inflammatory diseases with unknown physiopathology. For the first time, we report 3 cases of paradoxical chronic recurrent multifocal osteomyelitis after infliximab or adalimumab therapy during the course of Crohn disease. The patients complained of bone pain without joint involvement. At the time of diagnosis of paradoxical reaction, all patients were in remission due to anti-TNFα efficiency. Trough levels of anti-TNFα were in the expected range, and there were no anti–anti-TNFα antibodies. The duration of treatment was between 2 and 26 months. Other causes of CRMO were excluded. All patients recovered after discontinuation of infliximab (n = 2) or adalimumab (n = 1). The increasing use of these therapies leads to new descriptions of paradoxical effects, which clinicians should be aware of.

Clinical characteristics of pediatric synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome: the first Chinese case series from a single center.

Pediatric SAPHO syndrome is regarded as the equivalent of chronic recurrent multifocal osteomyelitis or chronic non-bacterial osteomyelitis. This study aimed to evaluate the clinical features and treatment options for Chinese pediatric patients with SAPHO syndrome. We conducted a single-center, retrospective study on a sample of 24 pediatric patients with SAPHO syndrome who were diagnosed at Peking Union Medical College Hospital from April 2014 to August 2018. The demographic, clinical, laboratory, imaging, histological, and therapeutic data were collected and analyzed. A total of 15 boys and 9 girls were included. The mean age of onset of bone and skin symptoms was 11.7 ± 3.8 and 14.4 ± 2.7years, respectively. The mean follow-up period was 39.2months. Seventeen patients had skin manifestations (46% had severe acne, 100% were boys; 21% had palmoplantar pustulosis, 100% were girls). Bone lesions were localized in four of the following major regions: anterior chest wall (42%), mandible (29%), peripheral bones (50%), and spine and sacroiliac joints (21%). Six patients had been treated with non-steroidal anti-inflammatory drugs, 10 with bisphosphonate, 10 with a tumor necrosis factor-α antagonist, and 1 with glucocorticoids, with variable responses. A total of 70% of the patients had complete remission after bisphosphonate or TNF-α antagonist therapy. Pediatric patients with SAPHO syndrome have different characteristics from other cohorts in the sex ratio, frequency of mandibular involvement, and sex distribution of skin lesions. Bisphosphonate and TNF-α antagonists show a favorable response in pediatric SAPHO syndrome treatment. Key points •Being the first study that describes an Asian pediatric SAPHO case series. •Chinese pediatric patients with SAPHO syndrome have different characteristics from Chinese adult patients and Caucasian pediatric patients.

Comment on: The conundrum of juvenile spondyloarthritis classification: Many names for a single disease? Lesson learned from an instructive clinical case

Dear Editor, We read with great interest the paper titled “The conundrum of juvenile spondyloarthritis classification: Many names for a single disease? Lesson learned from an instructive clinical case” by Maniscalco et al1 which emphasizes the complexity of the clinical phenotypes of juvenile spondyloarthropathies (JSpA). All pediatric rheumatologists face these evolving phenotypes of these groups of diseases in their daily practice. To handle these classificational dilemmas, several classification criteria have been proposed for JSpA.2-4 The most recent one, International League of Associations for Rheumatology (ILAR) classification criteria for juvenile idiopathic arthritis (JIA), does not mentioned JSpA as a discrete subgroup and classifies these groups of diseases under three main groups: enthesitis-related arthritis, psoriatic arthritis and undifferentiated arthritis.2 The main concerns about these criteria are: the certain phenotypes of JSpA like inflammatory bowel disease-related arthritis, reactive arthritis were not included in these criteria, and some of the patients are classified as undifferentiated arthritis because of patients fulfilling two subtypes of JIA. It is obvious that these classification criteria are insufficient to reflect all phenotypes of JSpA and there is apparently a need for new sets of criteria.5 The nomenclature for juvenile spondyloarthropathies is not well-defined and still remains enigmatic. This term mainly encompasses enthesitis-related arthritis, psoriatic arthritis, juvenile ankylosing spondylitis, inflammatory bowel disease-related arthritis and reactive arthritis.6, 7 Contrary to adult SpA, JSpA rarely involves the axial skeleton in the early stages of the disease and it usually presents with asymmetric oligoarthritis of lower extremity joints and enthesitis. Therefore, enthesitis-related arthritis can be seen as an early presentation of JSpA. In addition to mentioned diseases, it is also shown that clinical features of JSpA can be seen in the course of familial Mediterranean fever (FMF) and Mediterranean fever gene mutation may be a susceptibility factor for enthesitis-related arthritis especially in regions endemic for FMF.8 In our cohort of patients with FMF, 10.2% of children also fulfilled classification criteria for JSpA.8 Moreover, chronic recurrent multifocal osteomyelitis (CRMO) was suggested to be an unusual form of SpA by several authors and Vittecoq et al9 showed that some of the patients with CRMO developed SpA. The insightful report by Maniscalco et al1 also supports this perspective. In adult patients, rheumatoid arthritis which is the most common cause of adult chronic arthritis and ankylosing spondylitis are well-defined as two distinct phenotypes and both of them have highly accepted classification criteria. In contrast, JSpA is considered under the JIA umbrella in ILAR classification criteria. Yet, this classification criteria obviously are not sufficient to cover this broad spectrum of JSpA (the reasons mentioned above). It is difficult to distinguish between oligoarticular JIA and JSpA especially in the early stages of disease and pediatric rheumatology societies should focus on establishing clearer definitions for JIA and JSpA and developing the new classification criteria which cover all frameworks of JSpA as a distinct disease. We think this approach will not only provide expanded covering but also, better understanding between pediatric and adult rheumatologists. No author of this paper has a conflict of interest, including specific financial interests, relationships and/or affiliations relevant to the subject matter or materials included.