慢性再発性多発性骨髄炎

BACKGROUND: Bone marrow abnormalities are frequent radiological findings with a broad spectrum ranging from physiological conversion/reconversion to malignant infiltration. OBJECTIVE: This article summarizes important differential diagnoses of malignant bone marrow lesions and presents a practical diagnostic approach. MATERIAL AND METHODS: Narrative review based on the current literature, focusing on magnetic resonance imaging (MRI), computed tomography (CT) and supplementary techniques, such as chemical-shift imaging (CSI), Dixon sequences, diffusion-weighted imaging (DWI) and positron emission tomography CT (PET/CT). RESULTS: Non-fat-suppressed T1-weighted MRI is central for bone marrow assessment. A signal intensity lower than skeletal muscle or intervertebral discs argues against simple reconversion and should raise the suspicion of infiltration. The CSI and Dixon techniques help differentiate benign mimics by demonstrating intralesional fat. Important differential diagnoses include metastases, leukemia, lymphomas, myeloproliferative disorders, multiple myeloma, reconversion, bone infarcts, chronic nonbacterial osteitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO), Langerhans-cell histiocytosis (LCH), enostosis and osteomyelitis. CONCLUSION: The diagnosis requires integration of imaging patterns, fat content, mineralization, age, clinical context, tumor history and course. In unclear or aggressive findings, imaging follow-up or biopsy is required.

Chronic recurrent multifocal osteomyelitis (CRMO) and chronic nonbacterial osteomyelitis (CNO) are autoinflammatory diseases characterised by sterile bone inflammation. Patients with CNO or CRMO often complain about pain in the extremities, although several unusual manifestations have been reported. We report four paediatric cases of CNO/CRMO, demonstrating marked clinical variability in symptom onset and disease course. All patients presented with bone pain during their disease course, whereas unusual manifestations such as fever of unknown origin prior to the bone pain and cervical pain were confirmed. The diagnosis was established based on clinical features and by ruling out malignancy and infection through biopsy and culture. All patients received nonsteroidal anti-inflammatory drugs as initial therapy, and one required additional treatment with oral methotrexate and adalimumab. Serum cytokine analysis was performed in three cases, revealing elevated levels of both pro- and anti-inflammatory cytokines, such as interleukin-6, interleukin-10, and interleukin-33 in the pretreatment state. These cases underscore the clinical heterogeneity of CNO/CRMO.

PURPOSE OF REVIEW: To review and highlight key research findings in children and adults with chronic nonbacterial osteomyelitis (CNO). RECENT FINDINGS: Recent studies highlight substantial progress in CNO. Emerging data supports the existence of distinct phenotypic clusters in children and adults, along with recognition of extraosseous manifestations associated with greater disease severity and biologic use. New EULAR/ACR classification criteria and expert consensus recommendations represent important progress toward improving patient care. Administrative data is promising for cohort building and epidemiologic research in CNO. Recent work has identified key health domains impacting patients, highlighting the multidimensional nature, and reduced quality of life in CNO. Genetic and biomarker studies provide insight into inflammatory pathways. Advances in imaging and disease activity assessment emphasize the limitations of clinical measures alone, with composite measures providing improved performance. Reports of sarcopenia, and bone microarchitecture abnormalities suggest additional information may be gleaned from imaging. Finally, expanded therapeutic options are being used in recalcitrant cases suggesting that targeting interleukin (IL)-17/IL-23/Janus kinase pathways need to be tested in controlled studies to determine their place in treatment of CNO. SUMMARY: There is encouraging progress in CNO, with research efforts expanding our understanding of this disease across the age spectrum, with the ultimate goal of improving patient care.

BACKGROUND: Chronic non-bacterial osteomyelitis (CNO), also referred to as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disorder in children and adolescents. Bone pain is the most common presenting symptom, whereas prolonged recurrent fever of unknown origin is uncommon and may mimic infection or malignancy, leading to extensive diagnostic evaluations, including invasive procedures. CASE PRESENTATION: We report a 12-year-old girl who presented with recurrent fever as the predominant symptom, accompanied by delayed and intermittent musculoskeletal pain. Extensive infectious, rheumatologic, and oncologic investigations, including repeated cultures, metagenomic next-generation sequencing, and bone marrow examination, were unrevealing. Magnetic resonance imaging demonstrated multifocal bone marrow edema, and positron emission tomography-computed tomography showed multifocal FDG-avid skeletal lesions, with a maximum SUV of 6.85 among the focal skeletal lesions, raising concern for malignancy. Histopathological examination of a femoral bone biopsy revealed lymphoplasmacytic infiltration with focal fibrosis and no evidence of infection, granulomatous inflammation, necrosis, or malignancy. Based on the clinical course, imaging findings, exclusion of infection and malignancy, and histopathological findings, a diagnosis of CNO/CRMO was established. The patient improved after stepwise treatment with naproxen, methotrexate, and prednisone. CONCLUSION: This case illustrates an uncommon fever-dominant presentation of pediatric CNO/CRMO with multifocal skeletal lesions mimicking malignancy. CNO/CRMO should be considered in children with fever of unknown origin accompanied by delayed musculoskeletal symptoms or multifocal bone marrow lesions. In typical cases, biopsy may be avoided when clinical and imaging findings are characteristic; however, in atypical presentations with systemic symptoms and malignancy-like imaging findings, bone biopsy may remain necessary to exclude infection and neoplastic disease.