Chronic Nonbacterial Osteomyelitis Research Articles

Chronic Nonbacterial Osteomyelitis, Hidradenitis Suppurativa, and SAPHO Syndrome

Introduction: Synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome may represent one side of a spectrum of disease that also includes chronic nonbacterial osteomyelitis. Case: A 23-year-old male with bone pain in the anterior chest, shoulder, clavicles, left elbow, and left ankle presented to rheumatology clinic after multiple evaluations for infectious osteomyelitis. Imaging and deep bone biopsies of affected areas were consistent with chronic osteomyelitis, with labs notable for elevated erythrocyte sedimentation rate, C-reactive protein, and positivity for HLA-B27. A full skin exam was consistent with hidradenitis suppurativa, and he was started on infliximab and methotrexate with improvement in both his osteoarticular and skin symptoms. Conclusions: Patients presenting with features of follicular occlusion or neutrophilic dermatoses in conjunction with bone pain should be evaluated for SAPHO/CNO. In patients with SAPHO/CNO with vertebral involvement, bisphosphonates in addition to anti-inflammatory medications (such as methotrexate and TNF-inhibitors) can be effective.

Chronic secondary orofacial pain as the first symptom of chronic non-bacterial osteomyelitis in the mandible: a case report and literature review

Chronic non-bacterial osteomyelitis clinically manifests with pain, swelling and limitation of movement. When it affects the jaws, it can cause pain, similar to other orofacial conditions, requiring a correct differential diagnosis. The objective of this study was to report a clinical case of chronic secondary orofacial pain as the first manifestation of an inflammatory bone disease located in the mandible, in addition to discussing the diagnostic hypotheses, the pathophysiological aspects and the therapy. A 21-year-old male patient came to the service complaining of pain in the mandible, preauricular and temporal regions bilaterally with one year of evolution, associated with anterior open bite and psychological impairment. So, it was chronic orofacial pain secondary to non-bacterial osteomyelitis with a high rate of bone remodeling. Elevation of pro-inflammatory cytokines can lead to an increased power cycle of nociceptive signaling, chronic inflammation, and bone loss. Pro-inflammatory cytokines that originate in neuronal and glial cells can trigger effects such as chronic hyperexcitability, changes in the phenotypic expression of nociceptors and abnormal processing of noxious signals. The patient is still undergoing treatment and without pain. Careful assessment, ordering tests and multidisciplinary investigation are essential in the care of patients with chronic and complex orofacial pain.

Chronic non-bacterial osteomyelitis (CNO) and chronic recurrent multifocal osteomyelitis (CRMO) with a focus on pamidronate therapy.

Chronic recurrent multifocal osteomyelitis (CRMO), also called chronic nonbacterial osteomyelitis (CNO) or nonbacterial osteomyelitis (NBO), is a rare autoinflammatory bone disease of unknown etiology. However, the number of patients properly diagnosed would increase with better knowledge of the disease. In this regard, whole-body magnetic resonance imaging (WB MRI) has been found to be a better predictor of active lesions than clinical examination. Importantly, the RINBO index (radiologic index for NBO) quantifies the involvement based on the WB MRI. Further, a chronic nonbacterial osteomyelitis MRI scoring (CROMRIS) has been developed as an online tool for assessing WB MRI. The therapy consists of non-steroidal anti-inflammatory drugs (NSAIDs), bisphosphonates (pamidronate, zoledronate, etc.) and other drugs, including biologics. Pamidronate is an appropriate and safe therapy. The first pilot prospective randomised controlled trial (RCT) on pamidronate vs. placebo was carried out in adults. No RCT has been done in children yet. Besides RCTs, there are a number of issues to be explored in future, i.e. predictors of therapy effect, optimal therapy duration, predictors of therapy discontinuation and evaluation of optimal therapy protocol. Recently, the CNO clinical disease activity score (CDAS) was constructed and validated but the classification criteria are still being developed. As collaboration on this rare disease is essential, a prospective Chronic Nonbacterial Osteomyelitis International Registry (CHOIR) was established to generate future comparative effectiveness research data.

P019 Comparison of newly proposed chronic nonbacterial osteomyelitis classification criteria to previous diagnostic criteria

Abstract Background/Aims Chronic nonbacterial osteomyelitis (CNO) is an aseptic autoinflammatory bone disease of unknown etiology. This diagnosis can be delayed due to the non-specific nature of symptoms and normal imaging studies. New classification criteria were proposed in 2022. This study seeks to validate these new classification criteria by comparing them to previous diagnostic criteria in a cohort of known CNO patients. Methods This is a retrospective case-series of pediatric patients diagnosed with CNO (n = 39) between 2012 and 2023 in Virginia, USA. The newly proposed classification criteria (Table 1) was applied to this cohort. The entry criteria of chronic bone pain, age <18 years, abnormal radiograph and/or MRI were used prior to applying the newly proposed classification criteria. The 2008 Jansson diagnostic criteria and 2016 Bristol diagnostic criteria were also applied to the cohort for comparison and further validation. The clinical manifestations, laboratory results, and imaging studies that lead to a diagnosis of CNO were reviewed. Results The average age of diagnosis was 10 (range 2-17) years-old with the average time between onset of symptoms to confirmed clinical diagnosis being 24 (range 1-120) months. The most common presenting symptoms were bone pain (100%) and arthritis (49%). Evidence of radiographic abnormalities leading to CNO diagnosis was found with regional MRI (64%), bone scan (44%) with some requiring full body MRI (31%). Only one patient did not meet the new classification criteria (1/39; 3%) because of age <3 years, fever and elevated ESR which together gave less than the required 55 points for criteria fulfillment. One different patient (1/39; 3%) did not meet both the Bristol and Jansson criteria because of unifocal disease and lack of bone biopsy. Conclusion This retrospective chart review validates the newly proposed classification criteria for CNO. Older diagnostic criteria (Jansson and Bristol) both require advanced imaging and at times bone biopsy for fulfillment. We conclude that the newly proposed criteria is easy to apply even in the absence of a bone biopsy or advanced imaging studies. The newly proposed criteria will aid in the development of a homogeneous cohort for future studies about CNO. Disclosure A.M. Patel: Member of speakers’ bureau; ABBVIE, AMGEN, SANOFI. K.S. Lee: None. A.J. Kim: None.

A rare condition underlying childhood back pain: chronic nonbacterial osteomyelitis

A rare condition underlying childhood back pain: chronic nonbacterial osteomyelitis

Successful treatment of erythema nodosum with salazosulfapyridine in a 9-year-old patient with chronic non-bacterial osteomyelitis.

We report a 9-year-old Japanese girl with chronic non-bacterial osteomyelitis (CNO) accompanied by recurrent erythema nodosum (EN) which was successfully treated with salazosulfapyridine (SASP). She was referred to our hospital because of recurrent erythema on her lower extremities and persistent knee and ankle arthralgia, which had been present for approximately one year. Although naproxen, a nonsteroidal anti-inflammatory drug (NSAID), was initiated, her symptoms frequently recurred. Magnetic resonance imaging demonstrated multiple distinct high-intensity signals in the talus bones suggestive of multiple bone edemas. Additionally, a histological examination of erythematous lesions was consistent with the histopathological findings of EN. She was diagnosed as having CNO complicated by EN, and received 250 mg/day of SASP as a second-line treatment, which showed partial response of both skin and bone lesions. Following increase in the dose of SASP to 500 mg/day resulted in complete remission of her skin and bone lesions. In conclusion, our findings suggest that SASP is effective not only for CNO bone lesions but also for EN. SASP could serve as a second-line therapeutic option at least for some cases of CNO complicated by EN refractory to NSAIDs.

Diagnostic Role of FDG PET/CT in Pediatric Patients With Chronic Recurrent Multifocal Osteomyelitis.

Chronic recurrent multifocal osteomyelitis (CRMO), or chronic nonbacterial osteomyelitis, is difficult to diagnose. The accurate diagnosis of CRMO relies on comprehensive imaging examinations because of its multifocal nature. In this regard, 18 F-FDG PET/CT has demonstrated significant utility in inflammatory diseases. This study tries to determine the value of FDG PET/CT in the evaluation of CRMO. We retrospectively collected imaging data from pediatric CRMO patients who underwent FDG PET/CT scans. Lesions exhibiting abnormal metabolism with/without structural abnormalities on FDG PET/CT were identified as CRMO lesions, and their location and SUV max were recorded. A total of 21 pediatric patients with CRMO were included in this study. The median age at diagnosis was 9.4 years. Total 131 foci of abnormal activity were identified using FDG PET/CT imaging. The distribution pattern showed a higher prevalence of lower limbs and pelvis involvement. Among all identified lesions, abnormalities were detected on both PET and CT images of 93 lesions, whereas exclusively positive findings on 18 F-FDG PET alone were observed for 38 of them. Our study findings suggest a higher prevalence of lesions in the bones of the lower limbs and pelvis among children with CRMO. Compared with CT scans, FDG PET exhibits superior sensitivity in detecting these lesions.

Chronic non-bacterial osteomyelitis associated with psoriasis.

Chronic non-bacterial osteomyelitis associated with psoriasis.

Musculoskeletal symptoms and their impact on health-related quality of life in chronic nonbacterial osteomyelitis patients

IntroductionChronic non-bacterial osteomyelitis (CNO) is a rare, non-infection- related inflammatory disorder that affects children and teens. Clinical manifestations of CNO range widely from moderate, time-limited, monofocal inflammation of the bone to extreme multifocal or chronically active inflammation of the bone.ObjectivesThe main aim of this study was to explore the correlation between musculoskeletal (MSK) symptoms and health-related quality of life (HRQoL) in patients with CNO.MethodsChildren and adults with CNO and their parents were asked to answer a web-based survey. The survey consisted of multiple questions centered around demographic, clinical and therapeutic data, MSK discomfort form based on the Nordic MSK Questionnaire and HRQoL based on Pediatric Quality of Life Inventory-4 (PedsQL-4) and PedsQL rheumatology module. The inclusion criteria included diagnosis of CNO before the age of 18. Patients who had malignancies or any chronic rheumatic, MSK, neurological disease prior to CNO onset were excluded.ResultsThere was a total of 68 participants, mostly females (66.2%), with median age 14 years and median disease duration 4.75 years. The median number of bones affected by CNO was 5 and ranged from 1 to 24 bones. Among the studied patients, 45 patients (66.2%) had MSK manifestations at the last month. The most commonly affected part was ankle and feet (26.5%). Regarding HRQoL, patients with MSK manifestations had lower scores than did patients without in PedsQL-4 (p < 0.001) including domains of physical functioning (p < 0.001), emotional functioning (p = 0.033), social functioning (p < 0.001) and school functioning (p = 0.007) in addition to lower scores in PedsQL rheumatology module (p < 0.001) including domains of pain and hurt (p < 0.001), daily activities (p < 0.001), treatment (p = 0.035), worry (p = 0.001) and communication (p < 0.001).ConclusionMSK manifestations have a negative impact on HRQoL in CNO patients. So, early identification and treatment are highly recommended.

Chronic non-bacterial osteomyelitis of the mandible – orthodontic considerations and management: A case report

This case report describes the orthodontic management of a case of chronic non-bacterial osteomyelitis (CNO) of the mandible, a rare non-infective variant of osteomyelitis that exhibits a marked predilection in children and adolescents. The patient presented with a unilateral facial swelling associated with fluctuating pain. Radiographic examination, along with tissue biopsy and culture, as well as multispecialty input, led to confirmation of the diagnosis. There was no clear aetiological factor and pharmacological, symptomatic management was indicated. CNO requires multidisciplinary input, with good interspecialty communication and discussion, for an accurate diagnosis. Orthodontic management should be considered on a case-by-case basis, with tailored aims appropriate for each patient.

P2RX7 gene variants associate with altered inflammasome assembly and reduced pyroptosis in chronic nonbacterial osteomyelitis (CNO)

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.

Collaborative approach to paediatric chronic non-bacterial osteomyelitis of the mandible: Great Ormond Street Hospital case series

This paper outlines a 10-patient case series of chronic non-bacterial osteomyelitis (CNO) of the mandible at a tertiary paediatric hospital in the UK. Our findings highlight the homogeneous presenting signs and symptoms of an intermittently painful, swollen angle and ramus of the mandible. We present the typical laboratory investigative findings (normal inflammatory markers) and imaging appearances (sclerosis and periosteal oedema). Our paper outlines an investigation protocol, including recommendations for extraoral bone biopsies and systemic magnetic resonance imaging (MRI). We explain the importance of multidisciplinary care, with combined care by rheumatologists and infectious disease specialists. Finally we demonstrate the efficacy of our treatment algorithm for oral non-steroidal anti-inflammatory drugs (NSAIDs), and in those cases refractory to NSAIDS, intravenous pamidronate. This paper provides a useful addition to the literature by informing OMF surgeons of this rare condition and given the clinical equipoise in treatments, it can hopefully guide clinicians in an investigation pathway and management protocol.

P490 Prevalence and clinical features of chronic nonbacterial osteomyelitis in a nationwide cohort of children with inflammatory bowel diseases

Abstract Background Among musculoskeletal extraintestinal manifestations (EIM), the association between IBD and a rare autoinflammatory condition, chronic nonbacterial osteomyelitis (CNO), has been reported. The primary objective of our study was to report the clinical characteristics and the disease course of a cohort of patient with concurrent diagnosis of CNO and IBD. The secondary outcome was to define the prevalence of CNO in a nationwide cohort of patients with IBD. Methods This is a retrospective, multicenter study based on the Italian Society of Gastroenterology, Hepatology, and Pediatric Nutrition (SIGENP) IBD National Registry. The diagnosis of CNO was defined as the presence of uni- or multifocal bone inflammatory lesions with suggestive radiological or histopathological characteristics, having excluded infectious, oncological, or other inflammatory conditions. All patients under 18 years of age with a combined diagnosis of IBD and CNO identified in the registry were included. Results 18 patients with a combined diagnosis of CNO and IBD out of 4229 patients with IBD were identified, with an overall prevalence of 0.4%. 15 (83.3%) patients were male. Median age at IBD diagnosis was 10.1 years (IQR: 6.16 years), whereas median age at CNO diagnosis was 11.7 years (IQR: 6.31 years). The most frequently reported IBD phenotype was CD (13 patients, 72.2%), followed by IBD-U (3 patients, 16.7%) and UC (2 patients, 11.1%). The diagnosis of concurrent CNO was more common in patients affected by CD than in those affected by either UC or IBD-U (13/1843, 0.7% vs 5/2886, 0.2%, p=0.01). Similarly, the occurrence of CNO was more frequent in male gender when compared to female one (15/2312, 0.6% vs 3/1917, 0.1%, p=0.01). All the patients had multifocal bone involvement; 2 (11.1%) developed subsequently dermatological manifestations consistent with SAPHO syndrome. In 8 patients (44.4%) IBD onset preceded CNO diagnosis, in 6 (33.3%) IBD onset followed CNO diagnosis, whereas in the remaining 4 patients (22.2%) the diagnosis of IBD and CNO was concomitant. Table 1. summarizes therapeutic approach to both conditions in each of the patient identified in our case series. At the end of follow-up, 14 (77.8%) patients had achieved IBD clinical and biochemical remission. Ten (55.6%) patients achieved clinical and radiological remission of bone lesions, 6 (32.3%) had achieved clinical remission but showed persistence of bone lesions at magnetic resonance imaging (MRI), 2 (11.1%) had persistence of both clinical and radiological activity. Conclusion Our findings support the hypothesis that CNO disease spectrum can be considered a rare extraintestinal manifestation of IBD, with a low but still non-negligible prevalence.

Imaging of lower extremity infections: predisposing conditions, atypical infections, mimics, and differentiating features.

Imaging evaluation for lower extremity infections can be complicated, especially in the setting of underlying conditions and with atypical infections. Predisposing conditions are discussed, including diabetes mellitus, peripheral arterial disease, neuropathic arthropathy, and intravenous drug abuse, as well as differentiating features of infectious versus non-infectious disease. Atypical infections such as viral, mycobacterial, fungal, and parasitic infections and their imaging features are also reviewed. Potential mimics of lower extremity infection including chronic nonbacterial osteomyelitis, foreign body granuloma, gout, inflammatory arthropathies, lymphedema, and Morel-Lavallée lesions, and their differentiating features are also explored.

Garrè Sclerosing Osteomyelitis of the Clavicle: Clinical Results after Clavicular Resection.

(1) Background: Chronic non-bacterial osteomyelitis (CNO), also known as sclerosing osteomyelitis of Garrè, is a rare inflammatory bone disease with a specific clinical picture, uncertain pathogenesis, and no consensus on an effective treatment. Most frequently affecting other long bones, CNO may rarely involve the clavicle. The aim of this study was to present the results of a series of patients affected by CNO of the clavicle treated with total and partial clavicula resection. In addition, a literature review of different types of treatment of CNO was performed. (2) Methods: We retrospectively reviewed three patients with Sclerosing Osteomyelitis of Garre' of the clavicle treated with partial resection of the clavicle (one) and with total clavicular resection (two). (3) Results: Patients (two female and one male) were an average age of 35.7 years at the time of the operation. At the 4-year follow-up, the mean active ROM was: 143° forward flexion, 133° abduction, 42° external rotation with an internal rotation of two patients at the interscapular level and one patient at the lumbosacral junction. The mean ASES score was 92/100 (range 87-100). In the literature review, after screening the abstracts and full texts for eligibility, 34 studies met the inclusion criteria. Conclusions: Partial or total clavicular resection resulted an effective treatment of CNO of the clavicle. The procedure seems to be particularly indicated after the failure of more conservative treatments.

Preferential involvement of the pelvis and hips along with active sacroiliitis in chronic nonbacterial osteomyelitis: MRI of 97 patients from a single tertiary referral center.

To present MRI distribution of active osteitis in a single tertiary referral center cohort of patients with chronic nonbacterial osteomyelitis (CNO). Two musculoskeletal radiologists retrospectively reviewed MRI examinations of all patients with a final clinical diagnosis of CNO over 15years. Sites of active osteitis at any time during the course of disease were divided into seven groups: (A) mandible, sternum, clavicles, or scapulas; (B) upper extremities; (C) subchondral sacrum and ilium immediately subjacent to sacroiliac joints (active osteitis denoting "active sacroiliitis" here); (D) pelvis and proximal 1/3 of femurs (excluding group C); (E) bones surrounding knees including distal 2/3 of femurs and 1/2 of proximal tibias and fibulas; (F) distal legs (including distal 1/2 of tibias and fibulas), ankles, or feet; (G) spine (excluding group C). Temporal changes of lesions in response to treatment (or other treatment-related changes such as pamidronate lines) were not within the scope of the study. Among 97 CNO patients (53 males [55%], 44 females; age at onset, mean ± SD, 8.5 ± 3.2years; age at diagnosis, 10.3 ± 3.3years), whole-body (WB) MRI was performed in 92%, mostly following an initial targeted MRI (94%). A total of 557 (346 targeted and 211 WB) MRIs were analyzed. Biopsy was obtained in 39 patients (40%), all consistent with CNO or featuring supporting findings. The most common locations for active osteitis were groups D (78%; 95% CI 69‒85%) and C (72%; 95% CI 62‒80%). Pelvis and hips were preferentially involved in this cohort of CNO patients along with a marked presence of active sacroiliitis. When suggestive findings of CNO are identified elsewhere in the body, the next targeted site of MRI should be the pelvis (entirely including sacroiliac joints) and hips, if whole-body MRI is not available or feasible. • Heavy reliance on MRI for diagnosis of CNO underscores the importance of suggestive distribution patterns. • Pelvis and hips are the most common (78%) sites of CNO involvement along with active sacroiliitis (72%). • Pelvis including sacroiliac joints and hips should be targeted on MRI when CNO is suspected.

Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Doenças autoinflamatórias: um estudo multicêntrico latino-americano de acordo com o sexo e a idade

ABSTRACT Objective: To evaluate autoinflammatory diseases (AID) according to age at diagnosis and sex, and response to therapy in a large population. Methods: This is a cross-sectional observational study of a Latin American registry using a designed web system for data storage, collected between 2015 and 2018. Any altered findings during follow-up were recorded. The forms were translated into Portuguese and Spanish, including demographic, clinical, laboratory, genetic and treatment characteristics. Results: We included 152 patients, 51.3% male and 75% Caucasian. The median age at disease onset was 2.1 years (0–15.6 years) and median age at diagnosis 6.9 years (0–21.9 years); 111 (73%) were children (0–9 years old), and 41 (27%) were adolescents and young adults (AYA) (10–21 years old). Periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA) occurred in 46/152 (30%), chronic non-bacterial osteomyelitis (CNO) in 32/152 (21%), and familial Mediterranean fever (FMF) in 24/152 (15.7%). PFAPA was significantly higher in young children than in AYA (38.7% vs. 7.3%, p&lt;0.001), while CNO were lower (13.5% vs. 41.5%, p&lt;0.001). The frequency of females was significantly higher in CNO (28.4% vs. 14.1%, p=0.031) and lower in FMF (8.1% vs. 23.1%, p=0.011). The most used drugs were glucocorticoids, non-steroidal anti-inflammatory drugs (NSAID), and colchicine. Glucocorticoids and colchicine treatment were used in all AID with good to moderate response. However, cryopyrin-associated periodic syndromes (CAPS) seemed unresponsive to glucocorticoids. NSAIDs and methotrexate were the main medications used to treat CNO. Conclusions: Differences among AID patients were observed in the LA population regarding sex and age at disease diagnosis.

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis); A Case of Backache in an Adolescent in Pakistan

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, Osteitis) syndrome is a group of rare auto-inflammatory disorders with a wide range of dermatological and osteoarticular manifestations. Different nomenclatures, like Chronic Recurrent Multifocal Osteoarthritis (CRMO) and Chronic Non-Bacterial Osteomyelitis (CNO), have been used in the past for the same disease, but SAPHO Syndrome has been the accepted terminology since 1990. An adolescent, 17 years of age, with a six-month history of inflammatory backache and fatigue, reported to a rheumatology clinic. His health assessment questionnaire- disability indexcame out to be two. Acne on physical examination raised inflammatory markers, and characteristic findings of SAPHO syndrome on bone scan suggest the disease. The patient was treated with an excellent response to bisphosphonates. The report highlights the importance of the evaluation of inflammatory backache in adolescents. SAPHO syndrome is an underdiagnosed disease. Therefore, more awareness of this disease among healthcare physicians is required.

Machine Learning Algorithm: Texture Analysis in CNO and Application in Distinguishing CNO and Bone Marrow Growth-Related Changes on Whole-Body MRI.

The purpose of this study is to analyze the texture characteristics of chronic non-bacterial osteomyelitis (CNO) bone lesions, identified as areas of altered signal intensity on short tau inversion recovery (STIR) sequences, and to distinguish them from bone marrow growth-related changes through Machine Learning (ML) and Deep Learning (DL) analysis. We included a group of 66 patients with confirmed diagnosis of CNO and a group of 28 patients with suspected extra-skeletal systemic disease. All examinations were performed on a 1.5 T MRI scanner. Using the opensource 3D Slicer software version 4.10.2, the ROIs on CNO lesions and on the red bone marrow were sampled. Texture analysis (TA) was carried out using Pyradiomics. We applied an optimization search grid algorithm on nine classic ML classifiers and a Deep Learning (DL) Neural Network (NN). The model's performance was evaluated using Accuracy (ACC), AUC-ROC curves, F1-score, Positive Predictive Value (PPV), Mean Absolute Error (MAE) and Root-Mean-Square Error (RMSE). Furthermore, we used Shapley additive explanations to gain insight into the behavior of the prediction model. Most predictive characteristics were selected by Boruta algorithm for each combination of ROI sequences for the characterization and classification of the two types of signal hyperintensity. The overall best classification result was obtained by the NN with ACC = 0.91, AUC = 0.93 with 95% CI 0.91-0.94, F1-score = 0.94 and PPV = 93.8%. Between classic ML methods, ensemble learners showed high model performance; specifically, the best-performing classifier was the Stack (ST) with ACC = 0.85, AUC = 0.81 with 95% CI 0.8-0.84, F1-score = 0.9, PPV = 90%. Our results show the potential of ML methods in discerning edema-like lesions, in particular by distinguishing CNO lesions from hematopoietic bone marrow changes in a pediatric population. The Neural Network showed the overall best results, while a Stacking classifier, based on Gradient Boosting and Random Forest as principal estimators and Logistic Regressor as final estimator, achieved the best results between the other ML methods.