Bacterial arthritis and osteomyelitis are usually acute diseases, which in this way differ from the often insidious course of nonbacterial osteomyelitis; however, there is often an overlap both in less acute courses of bacterial illnesses and also in nonbacterial osteitis. The overlapping clinical phenomena can be explained by similar pathophysiological processes. In bacteria-related illnesses the identification of the pathogen and empirical or targeted anti-infectious treatment are prioritized, whereas no triggering agent is known for nonbacterial diseases. The diagnostics are based on the exclusion of differential diagnoses, clinical scores and magnetic resonance imaging (MRI). An activity-adapted anti-inflammatory treatment is indicated.
UNASSIGNED: Die bakterielle Arthritis und Osteomyelitis sind in der Regel akute Erkrankungen, die sich dadurch von der oft schleichend verlaufenden nichtbakteriellen Osteomyelitis unterscheiden. Allerdings gibt es auch Überlappungen sowohl bei weniger akut verlaufenden bakteriellen Erkrankungen als auch bei nichtbakteriellen Knochenentzündungen. Die überschneidenden klinischen Phänomene sind durch ähnliche pathophysiologische Prozesse zu erklären. Während bei den bakteriell bedingten Erkrankungen die Erregergewinnung und empirische oder gezielte antiinfektiöse Therapie im Vordergrund stehen, ist für die nichtbakteriellen Erkrankungen kein auslösendes Agens bekannt. Die Diagnostik basiert auf dem Ausschluss von Differenzialdiagnosen, klinischen Scores und der MRT-Bildgebung. Eine aktivitätsadaptierte antiinflammatorische Therapie ist indiziert.

Chronic recurrent multifocal osteomyelitis (CRMO), an autoinflammatory bone disorder characterized by non-bacterial osteomyelitis causing recurrent multifocal bone lesions, is a well-known, yet uncommon pediatric condition that rarely affects adults; to date, it has never been diagnosed over the age of 75. The following report will discuss the first octogenarian diagnosed with CRMO and therefore represents an exceptionally rare presentation of a rare disease. An 83-year-old woman presented with progressive right shoulder, forearm, and hip pain, with associated weight loss and global weakness, requiring a wheelchair for mobility. Imaging revealed a pathologic right ulna fracture in addition to lytic lesions of the right proximal humerus and proximal femur. The clinical picture was thus that of a patient with probable multiple myeloma versus metastatic disease. After an extensive workup, however, the lesions were not malignant; histologic findings were instead suggestive of chronic osteomyelitis with negative cultures. Given the multifocal nature of this condition, combined with a lack of clinical symptoms of infection, a diagnosis of CRMO was rendered. The patient underwent intramedullary nailing of the right femur and splinting of the ulna, with a subsequent remarkable recovery to painless ambulation, complete union of the right ulna fracture, and resolution of the lytic lesions without receiving any targeted medical treatment. This case highlights the importance of maintaining CRMO on the differential for multifocal skeletal lesions, regardless of age. Performing a thorough workup with necessary imaging, biopsy, and culture are critical to establishing this diagnosis, which can only made as a diagnosis of exclusion.

OBJECTIVE: To report a statistical evaluation of symptomatology based on 56 cases of SAPHO syndrome and 352 non-SAPHO involvement cases, to propose a symptomatic scoring system in consideration of early warning for SAPHO syndrome.
METHODS: A cohort comprising 56 subjects diagnosed with SAPHO syndrome was reported, as well as 352 non-SAPHO involvement cases, including their chief complaints, skin manifestations, radiological findings, and laboratory tests. We systematically reviewed previous published five representative huge cohorts from different countries to conclude several specific features of SAPHO by comparing with our case series. The score of each specific index is based on respective incidence and comparison of two cohorts was performed.
RESULTS: In terms of complaint rates, all subjects of two cohorts suffered from osseous pain, which appeared in the anterior chest wall, spine, and limb which were calculated. In respect to dermatological lesions, SAPHO patients suffered from severe acne, and other patients (82.14%) accompanied with palmoplantar pustulosis. Having received radiological examinations, most SAPHO subjects rather than non-SAPHO involvement cases showed abnormal osteoarticular lesions under CT scanning and more detailed information under whole-body bone scintigraphy. Differences also emerged in elevation of inflammation values and rheumatic markers like HLA-B27. Based on our cases and huge cohorts documented, the early warning standard is set to be 5 scores.
CONCLUSIONS: SAPHO syndrome case series with 56 subjects were reported and an accumulative scoring system for the early reminder on SAPHO syndrome was proposed. The threshold of this system is set to be 5 points. Key Points • Fifty-six patients diagnosed by SAPHO syndrome with detailed symptoms and radiological findings were reported. • Comparison was made between the 56 SAPHO patients and 352 non-SAPHO involvement cases. • An accumulative scoring system for the early reminder on SAPHO syndrome was proposed and the threshold of this system is set to be five points.

Chronic nonbacterial osteomyelitis (CNO), an autoinflammatory bone disease primarily affecting children, can cause pain, hyperostosis and fractures, affecting quality-of-life and psychomotor development. This study investigated CNO-associated variants in P2RX7, encoding for the ATP-dependent trans-membrane K+ channel P2X7, and their effects on NLRP3 inflammasome assembly. Whole exome sequencing in two related transgenerational CNO patients, and target sequencing of P2RX7 in a large CNO cohort (N = 190) were conducted. Results were compared with publicly available datasets and regional controls (N = 1873). Findings were integrated with demographic and clinical data. Patient-derived monocytes and genetically modified THP-1 cells were used to investigate potassium flux, inflammasome assembly, pyroptosis, and cytokine release. Rare presumably damaging P2RX7 variants were identified in two related CNO patients. Targeted P2RX7 sequencing identified 62 CNO patients with rare variants (32.4%), 11 of which (5.8%) carried presumably damaging variants (MAF <1%, SIFT \"deleterious\", Polyphen \"probably damaging\", CADD >20). This compared to 83 of 1873 controls (4.4%), 36 with rare and presumably damaging variants (1.9%). Across the CNO cohort, rare variants unique to one (Median: 42 versus 3.7) or more (≤11 patients) participants were over-represented when compared to 190 randomly selected controls. Patients with rare damaging variants more frequently experienced gastrointestinal symptoms and lymphadenopathy while having less spinal, joint and skin involvement (psoriasis). Monocyte-derived macrophages from patients, and genetically modified THP-1-derived macrophages reconstituted with CNO-associated P2RX7 variants exhibited altered potassium flux, inflammasome assembly, IL-1β and IL-18 release, and pyroptosis. Damaging P2RX7 variants occur in a small subset of CNO patients, and rare P2RX7 variants may represent a CNO risk factor. Observations argue for inflammasome inhibition and/or cytokine blockade and may allow future patient stratification and individualized care.

Chronic nonbacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn\'s disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use and suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves a genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.

Spinal involvement by chronic non-bacterial osteomyelitis (CNO) has been increasingly reported in recent years, often being presented as a diagnostic dilemma requiring differential diagnosis with bacterial spondylodiscitis and/or neoplasia. This study was aimed at identifying the imaging features of CNO facilitating its differentiation from other spinal diseases. Two radiologists assessed the imaging studies of 45 patients (16 male and 29 female, aged from 6 to 75 years, 15 children) with CNO collected from 5 referential centers. Spinal lesions were found in 17 patients (2 children and 15 adults), most often in the thoracic spine. In children, the lesions involved short segments with a destruction of vertebral bodies. In adults, the main findings were prominent bone marrow edema and osteosclerosis, endplate irregularities, and ankylosing lesions extending over long segments; paraspinal inflammation was mild and abscesses were not observed. In both children and adults, the involvement of posterior elements (costovertebral and facet joints) emerged as an important discriminator between CNO and neoplasia/other inflammatory conditions. In conclusion, a careful inspection of imaging studies may help to reduce the number of biopsies performed in the diagnostic process of CNO.

We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient\'s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.

Chronic recurrent multifocal osteomyelitis (CRMO) is an underrecognized autoinflammatory disease affecting the skeletal system. Its vague symptoms are often first attributed to growing pains, infection, or malignancy, which can lead to a delay in diagnosis for days to years. Untreated CRMO has the potential to cause debilitating skeletal deformities, arthritis, and chronic pain; hence early recognition and treatment are paramount. MRI is the gold standard for diagnosis. Treatment consists of various antiinflammatory medications and may also include bisphosphonates if vulnerable skeletal sites are involved. Even when treated, the disease may have a relapsing course lasting years.

to evaluate whether the heterogeneous skin manifestations might influence the disease presentation and outcome of a cohort of SAPHO children.
the clinical, serological, imaging and therapeutic data of 14 SAPHO patients, followed between 2001 and 2022 at the Unit for Autoinflammatory diseases at the Gaslini Hospital, were reviewed. According to their cutaneous manifestations, patients were divided into 2 groups: the acne-hidradenitis suppurativa (HS) and the Palmo-Plantar Pustulosis (PPP) group. Data were retrieved from the Eurofever database.
all patients presented bone involvement characterized by Chronic Recurrent multifocal Osteomyelitis (CRMO): 8 patients presented acne-HS while 6 patients had PPP. In the PPP group, all patients were female, characterized by a prepuberal disease onset with osteoarticular manifestations, followed by the appearance of PPP in the following 6 months. This group responded well to the treatments. In the acne-HS group, 7/8 patients were male: the disease onset was characterized by skin manifestations in pubertal age, followed by osteoarticular manifestations in the following year. This group presented a severe refractory skin disease that required in most cases the addition of biological therapies. A literature review confirmed our data highlighting the association males-acne-puberal age and female-PPP-prepuberal age.
paediatric SAPHO patients should be mainly stratified according to their skin involvement. In fact, our data suggest that two different skin phenotypes may be identified in SAPHO: the first is constituted by prepuberal females with PPP and a prevalent osteoarticular involvement, while the second by puberal males with a difficult-to-treat acne-HS.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disease predominantly affecting the metaphyses of long bones and is usually seen in children. Although CRMO is generally a pediatric disease, it may also occur in adults. This may result in a delay in the diagnosis of adult-onset CRMO. This report presents an adult-onset female patient who presented with left leg pain followed by swelling in the right knee. The patient was initially started on colchicine treatment, but, due to unresponsiveness in the follow-up the patient, the treatment was switched to a combination of methotrexate and prednisolone. A satisfactory clinical recovery was achieved with these drugs. CRMO could be considered in the differential diagnosis of patients presenting with bone pain and joint complaints. Considering that the disease progresses with clinical flare-ups and remission periods, it should be kept in mind that patients should be followed closely and treatment can be changed.