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

Abstract

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.

Immunological Characterization of Chronic Nonbacterial Osteomyelitis (CNO) in Adults: A Cross‐Sectional Exploratory Study

“…2 and Table S1. ESR and CRP were higher in patients with ACW + vertebral involvement, as compared to ACW involvement alone (median [IQR] 33 versus 11 [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21] mm/hr for ESR, p < 0.01 and 11 (5)(6)(7)(8)(9)(10)(11)(12)(13)(14) versus 3.1 (1)(2)(3)(4)(5)(6)(7) mg/L for CRP, p = 0.024, Fig. 2).…”

“…Clinically, children with CNO, also known as chronic recurrent multifocal osteomyelitis (CRMO), may present with systemic symptoms of inflammation like fever, subfebrile temperature, or weight loss, whereas in adults this is rarely seen. ( 5 , 6 ) Biochemically, mild to moderate elevation of generic inflammation markers like C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are common in children, but hardly seen in adults. ( 7 , 8 ) Likewise, pediatric cytokine analyses have revealed increased expression of pro‐inflammatory cytokines, specifically interleukin (IL)‐6, IL‐17A, and tumor necrosis factor α (TNFα).…”

Case report: Child chronic nonbacterial osteomyelitis with rapid progressive scoliosis-an association with disease?

“…There is evidence that CNO may be caused by genetic factors ( 3 , 32 ). Our preliminary whole exome sequencing results suggest this patient has a LAMB3 (c.595G > A) gene variant which is a protein-coding gene in exon7.…”

A Successful Bisphosphonates Monotherapy in Spinal Form of Paediatric Chronic Recurrent Multifocal Osteomyelitis (CRMO)—Case Report

“…The lesions are located most frequently in lower extremities (ca. 20–50% of lesions), especially in the pelvis [ 9 , 10 ]. Spinal lesions are found less frequently, amounting to ca.…”

“…Spinal lesions are found less frequently, amounting to ca. 13–17% of lesions [ 9 , 10 ]. It is the latter localisation which is associated with compressive fractures and malformations, leading to the developmental problems [ 11 ].…”