The objective of this study was to confirm the presence of different disease phenotypes of paediatric SAPHO syndrome (pSAPHO) based on their skin manifestations in a large cohort of Italian patients.

Patients with pSAPHO were enrolled in the Eurofever Registry and the data retrospectively analysed. The patients were categorized according to their skin manifestations into an acne - hidradenitis suppurativa (Acne-HS) group and a palmoplantar pustulosis - psoriasis vulgaris (PPP-PV) group and were compared with patients without skin manifestations (chronic non-bacterial osteomyelitis, CNO). Comparisons of frequencies between groups were performed using the χ2 test or the Fischer's exact test.

A total of 54 pSAPHO patients with skin manifestations (35 Acne-HS, 19 PPP-PV) were enrolled and compared with 167 patients with chronic recurrent multifocal osteomyelitis (CRMO). In the Acne-HS group, 82.9% were males, in the PPP-PV, 84.2% were females, while in the chronic non-bacterial osteomyelitis (CNO) group, no gender differences were observed (P < 0.0001). The three groups differed significantly with respect to age at disease onset: Acne-HS median 13.3 years, PPP-PV median 10.2 years, CNO median 9.5 years (P = 0.0001). An axial pattern was more frequent in the Acne-HS (91.4%) group and the PPP-PV group (89.4%) compared with in the CNO group (46%) (P < 0.0001). Both the Acne-HS (82.9%) and the PPP-PV (63.2%) groups required a biologic therapy more frequently than the CNO group (36.8%), but patients with Acne-HS presented with a refractory skin disease requiring steroids and other lines of treatment, while PPP-PV responded well to biologics.

Our data have identified two different phenotypes of pSAPHO based on skin manifestations, with different age of onset, gender, and response to treatments. These two groups have peculiar clinical features that differ from those of the CNO group. A new classification encompassing these phenotypes is warranted.

To evaluate the long-term effectiveness of the combination of Iguratimod (IGU) and Alendronate for patients with Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome.

A prospective cohort study was conducted on patients diagnosed with SAPHO syndrome at Peking University Third Hospital and Beijing Jishuitan Hospital from 2017 to 2024. The initial treatment regimen comprised a combination of IGU and Alendronate. Patients who were followed up for >2 years were included in our study. We collected demographic data, clinical symptoms, recurrence rates, treatment duration and overall response to therapy for all patients.

Seventeen patients were recruited for our cohort, with a median (IQR) follow-up of 2.91 (2.34) years. The mean treatment duration was 39.10 months. Among patients with osteoarticular involvement (17/17), 35.30% (6/17) achieved complete improvement without any recurrence, 11.76% (2/17) showed partial improvement and 52.94% (9/17) experienced intermittent flares. For patients with skin involvement (11/17), 63.64% (7/11) achieved complete improvement, 27.27% (3/11) had partial improvement and 9.09% (1/11) experienced intermittent recurrence. Notably, 88.26% (15/17) regained complete independence and resumed work, and 94.12% (16/17) experienced alleviation of anxiety and insomnia. By the end of last follow-up, 52.94% (9/17) had ceased treatment after a mean duration of 25.22 months and 22.22% (2/9) of them encountered recurrence.

The combination of IGU and Alendronate as initial treatment may be effective for the long-term management of SAPHO syndrome. ∼41% of the patients could discontinue treatment after more than two years without recurrence.

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare autoinflammatory disease characterized by cutaneous manifestations and osteoarticular damage. The pathogenesis of SAPHO syndrome has not yet been elucidated, but studies have shown that the abnormal bone metabolism of patients with SAPHO syndrome is most likely due to localized infections that induce immune disorders in the body. Although no standardized treatment protocols exist, based on existing case studies and data from open studies, we propose that the treatment of SAPHO syndrome can be categorized into three areas according to the symptomatic manifestations of the disease: (1) control of focal infections using antibiotics and tonsillectomy; (2) administration of DMARDs to manage disease progression; and (3) bone remodeling therapy with bisphosphonates to address abnormal bone metabolism. Furthermore, a comprehensive treatment approach tailored to the clinical manifestations of the patient can effectively alleviate symptoms and enhance quality of life.

Osteomyelitis due to Cutibacterium acnes in the clavicle without a history of previous surgery is extremely rare and has been reported in one previous study. In this report, we delve into a case of clavicular osteomyelitis caused by C. acnes without the presence of hardware materials.

We report here a case of a 32-year-old female presented with spontaneous clavicular osteomyelitis due to C. acnes that failed with medical management. The Patient was successfully treated by surgical debridement and calcium sulfate filling that impregnated with local antibiotics.

This case demonstrates that clavicular osteomyelitis can be caused by C. acnes even without the presence of a device. Therefore, cultures from potential bone infections that yield C. acnes should not be dismissed as contaminants. Combining clinical and laboratory criteria with emerging microbiologic tests may enhance the predictive value of C. acnes diagnostic testing in the future.

Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a rare disease characterized by a sterile inflammatory osteitis and/or arthritis associated with a wide range of dermatological manifestations, such as acne, palmoplantar pustulosis, and psoriasis. This review, providing up-to-date knowledge on this disease, aims at informing researchers and clinicians to help them program future studies in order to improve patients' care. Due to the vast clinical heterogeneity that characterizes this disease, SAPHO syndrome has received various names; among these, chronic recurrent multifocal osteomyelitis represents the most used one. The various nomenclatures in use also reflect different approaches to its management. Indeed, considering the world-wide distribution and the vast onset age (from children to late adulthood), in addition to the multiform clinical presentation, its diagnosis and treatment are often challenging for clinicians. In this review, we provide valuable insights on SAPHO syndrome, delving into its many aspects: epidemiology, pathogenesis, clinical presentation, diagnosis, and classification. Most importantly, this paper addresses the continuously changing treatment panorama of this disease, from established drugs to newly introduced ones. Furthermore, a peculiar focus regards nonpharmacologic approaches, including traditional Chinese medicine, the apheresis technique, and surgery. Similarly, this review also discusses patients' lifestyle, including quality of life. To improve SAPHO syndrome's management, different knowledge gaps should be filled, such as its current epidemiology and pathogenesis. In turn, perfected knowledge in these fields could also advance research in therapy.

There is considerable practice variation in labelling, diagnosis and treatment of adults with sterile bone inflammation. We developed a expert consensus recommendations on the disease definition, diagnosis and treatment of this rare condition.

Systematic literature review and Grading of Recommendations, Assessment, Development and Evaluations-based appraisal of evidence, two Delphi surveys and three digital and in-person consensus meetings with a multidisciplinary expert panel and patient representatives.

A consensus disease definition was developed and the term 'chronic non-bacterial osteitis' (CNO) is proposed to describe adults with sterile bone inflammation. For initial imaging evaluation of adults with suspected CNO, the panel recommends MRI or otherwise CT combined with nuclear imaging. Whole-body imaging at initial evaluation can be considered for diagnostic and prognostic purposes. Suggested first-line treatment in adults with active CNO includes nonsteroidal anti-inflammatory drugs/cyclooxygenase 2-inhibitors. Second-line treatment preferably consists of intravenous bisphosphonates, and otherwise tumour necrosis factor-α inhibitors. Choice between them should be individualised, considering the presence of additional inflammatory features. The panel further discusses outcome measures, follow-up and management of adverse events and complications.

These expert consensus recommendations are intended to support healthcare professionals worldwide in their care for adults with CNO. They also lay the groundwork for establishing international patient registries, translational research lines and multicentre trials, all of which are urgently required.

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a rare inflammatory bone disorder with a remarkably low incidence. The condition's impact on the mandible is exceptionally uncommon, often resulting in a high rate of misdiagnosis and an extended duration of illness. The objective of this study was to assess patients with SAPHO syndrome in the mandible in across various stages and to dissect their distinctive features, aiming to provide future clinical experience for the disease.

A retrospective analysis was performed on a cohort of 17 patients diagnosed with SAPHO syndrome affecting the mandible at the Second Affiliated Hospital of Zhejiang University from January 2020 to March 2023. Data including clinical presentations, imaging characteristics, and laboratory results were collected.

The median age at disease onset was 25, with a diagnostic interval of 26 months. Notably, seven individuals were prepubescent (under the age of 14). Seven patients (41.18 %) exhibited polyostotic involvement, while eight patients (47.06 %) presented with dermatological manifestations either concurrently with or subsequent to the osseous lesions. Condyle involvement was identified in six patients (35.29 %), and bilateral mandibular affection was noted in an equivalent number. The majority of patients (sixteen patients, 94.12 %) reported symptomatic relief following treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). Glucocorticoids were instrumental in managing severe pain and extreme limitations in mouth opening. For patients with refractory disease, tumor necrosis factor-alpha (TNF-α) inhibitors, Janus kinase (JAK) inhibitors and bisphosphonates were employed. Ultimately, effective pain management was achieved in the entire cohort.

The diagnosis of SAPHO syndrome involving the mandible is exclusionary. It is important to improve diagnostic accuracy among oral and maxillofacial surgeons (OMFS), dentists, and rheumatologists to avoid unnecessary surgery and tooth extraction. TNF-α inhibitors, JAK inhibitors and bisphosphonates are recommended as third-line drugs.

Autoinflammatory bone diseases (AIBDs) constitute a recently identified subset of autoinflammatory diseases. These conditions are characterized by an exaggerated inflammatory response in the bones without any apparent etiology. Inflammatory bone lesions associated with AIBDs exhibit chronic inflammation, are typically culture-negative, and do not exhibit discernible microorganisms on histopathological examination. The most common and representative AIBD is chronic non-bacterial osteomyelitis (CNO), which is also known as chronic recurrent multifocal osteomyelitis. Another variant of CNO, which is typically observed in older teenagers or adults, is known as synovitis, acne, hyperostosis, pustulosis, osteitis syndrome. This condition is distinguished by its notable skin manifestations. Advancements in genetic research have led to the identification of three novel monogenic subtypes within the category of AIBDs. These include Majeed syndrome, pyogenic arthritis, pyoderma gangrenosum, and acne syndrome, and interleukin-1 receptor antagonist deficiency syndrome. Another monogenic AIBD, called cherubism, affects only the maxilla and mandible. Data on the diagnosis and treatment of these rare diseases are extremely limited. However, if not diagnosed and treated promptly, it can result in significant complications, including severe disability and mortality. Thus, it is imperative to maintain a high level of clinical awareness of these diseases. These rare diagnoses should be considered in patients with musculoskeletal complaints in whom no specific etiology can be identified or in patients with systemic manifestations such as cutaneous and gastrointestinal symptoms or fever. In such patients, the diagnostic process, which encompasses imaging and genetic studies, should be initiated promptly.

This review provides an overview of SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis), a rare autoinflammatory disease that primarily affects bones, skin, and joints. We conducted a search on Medline/PubMed using keywords such as SAPHO syndrome, chronic recurrent multifocal osteitis/osteomyelitis, and related terms. SAPHO syndrome is rare, with a reported frequency of 1 in 10,000 in the Caucasian population. However, the actual incidence of SAPHO syndrome is unknown, and the incidence of the disease is likely higher. The pathogenesis of SAPHO syndrome remains incompletely understood. Current evidence suggests that SAPHO results from a complex interplay between immune dysregulation, genetic susceptibility, and environmental factors. It's not clear if SAPHO syndrome is an autoimmune disease or an autoinflammatory disease, but current evidence suggests that it's more likely an autoinflammatory disease because of things like neutrophil hyperactivity, fewer natural killer (NK) cells, high levels of interleukin (IL)-1, and a good response to treatments that block IL-1. Osteo-articular (OA) involvement is a key clinical feature of SAPHO. It affects the anterior chest wall, axial skeleton, peripheral joints, mandible, long bones of the extremities, and pelvis. Dermatological involvement is a common target in SAPHO, with lesions observed in 60-90% of cases. Common skin lesions include psoriasis and acne, with hidradenitis suppurativa and neutrophilic dermatoses being less commonly seen. Other clinical findings include constitutional symptoms caused by systemic inflammation, such as fever, weight loss, and fatigue. There is no specific laboratory finding for SAPHO syndrome. However, during active disease, there may be an increase in positive acute phase markers, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement levels, mild leukocytosis, and thrombocytosis. Diagnosis is crucial for SAPHO syndrome, which lacks a specific diagnostic finding and is often underrecognized. A comprehensive evaluation of a patient's medical history and physical examination is crucial. Treatment options include non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, conventional and synthetic disease-modifying agents (cDMARDs and sDMARDs), biological therapies, bisphosphonates, and antibiotics. Biological treatments have emerged as a viable alternative for SAPHO patients who do not respond to conventional treatments.

SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis, osteitis syndrome) is a systemic inflammatory disease characterized by a combination of both osteoarticular and dermatological manifestations. We encountered an interesting case of a 54-year-old female patient who presented with symptoms of recurrent chest infections. Extensive investigations, including laboratory tests and imaging, were conducted with an initial suspicion of malignancy, but the patient was ultimately diagnosed with SAPHO. Treatment was initiated with a corticosteroid and an immunosuppressant, resulting in mild symptom improvement. This case emphasizes the importance of considering SAPHO syndrome in patients with unexplained musculoskeletal and dermatological symptoms, as early diagnosis and treatment can significantly impact patient outcomes.

Chronic nonbacterial osteitis (CNO) is a rare bone disease causing pain and functional impairment. We aimed to explore the application of physical therapy (PT) for adult CNO from the patients' and primary care therapists' perspective.

Cross-sectional study among the Dutch adult CNO cohort (1992-present). A survey on PT-use for axial spondylarthritis was adapted for CNO. Patients using PT in the past 2 years (recent PT-users) were asked about modalities, perceived effects, satisfaction, and preferences for provision. Their current physical therapists were invited to complete a self-developed survey covering therapy details and educational preferences.

80/199 invited patients and 14/16 invited therapists completed the survey respectively. 41 (51%) patients used PT for CNO in the preceding 2 years, 14 (18%) used PT >2 years back, and 25 (31%) never used PT. Recent PT-users (n=41) reported diverse treatment modalities, involving massage (61%), joint mobilizations (44%), breathing exercises (49%), muscle strengthening (32%) and counselling through of home-exercises (46%) and pain education (32%). 64% of all patients desired greater emphasis from physicians regarding the role of PT. Most therapists would appreciate referral letters with CNO-specific information (93%), and consultations with specialized therapists (86%).

In this study, two-third of adult CNO patients had -ever or recently- used PT, which involved variable therapeutic modalities. Most patients were receptive to a larger role of PT in CNO-management and most therapists preferred CNO-specific information to optimize their care. These findings provide a foundation for the development and systematic evaluation of CNO-specific PT.

In this study, we employed a large language model to evaluate the diagnostic efficacy of radiology reports of bone scintigraphy in the context of identifying SAPHO syndrome, and further examined the potential of such a model to augment the diagnostic procedure.

Imaging data and clinical information of 151 patients (105/46 women/men, mean age: 53.5 years) who underwent bone scintigraphy for suspected Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO) syndrome between January 2007 and December 2022 were retrospectively reviewed. ChatGPT-4.0 was used as the large language model. The diagnostic performance of the large language model was verified by comparing the cases judged to have SAPHO syndrome that fulfilled Kahn's classification criteria based on a combination of concise radiology reports and skin lesions such as palmoplantar pustulosis, with cases diagnosed with SAPHO syndrome by rheumatologists based on all clinical information.

The diagnostic accuracy of a large language model for analysing bone scintigraphy radiology reports in conjunction with information about skin symptoms, such as palmoplantar pustulosis, achieved a sensitivity of 83.5%, specificity of 69.4%, and an overall accuracy of 76.8%.

This research indicates the prospective value of extensive language models in scrutinizing radiology accounts from bone scintigraphy for the diagnosis of SAPHO syndrome.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an autoinflammatory disease whose acronymic name stands for the symptoms commonly seen in the disease. These symptoms typically occur simultaneously, in different combinations, in patients during exacerbations of the disease. SAPHO syndrome is a rare disease, most frequently seen in patients aged 30 to 50. It is estimated to be found in 1 in 10 000 persons in White populations, with an even lower incidence seen in non-White populations.

A post-menopausal woman with a medical history of SAPHO presented to the emergency department with left foot pain and chest pain with palpitation. She had chronic pustular rashes, located on the bilateral soles of the feet, bilateral palms, neck, and abdomen, which she stated appeared hours after the initial presentation of her pain. Chest X-ray readings showed osteitis and sclerosis of the sternocostoclavicular joint and first rib, a radiological finding of SAPHO syndrome. The patient was successfully treated with nonsteroidal anti-inflammatory drugs for pain relief and IV corticosteroids for the rheumatoid-like inflammatory aspect of SAPHO.

While SAPHO syndrome is a rare disease, it is important to be aware of its manifestations and symptoms, such as the patient's rash, foot and chest pain, in addition to the dermatological symptoms appearing simultaneously. An early diagnosis can provide patients with accurate and appropriate treatment.

Among 5 types of the Christie-Atkins-Munch-Petersen factor (CAMP) of Cutibacterium acnes, CAMP1 is highly expressed in phylotype II as well as IB, and thought to be a virulence factor of opportunistic but fatal blood, soft tissue, and implant-related infections. The target of a human single-chain variable antibody fragment (scFv), recently isolated from a phage display library, has been identified as CAMP1 of phylotype II, using immunoprecipitation followed by mass spectrometry, phage display peptide biopanning, 3D-modelling, and ELISA. The IgG1 format of the antibody could enhance phagocytosis of C. acnes DMST 14916 by THP-1 human monocytes. Our results suggest that the antibody-dependent phagocytosis process is mediated by the caveolae membrane system and involves the induction of IL-1β. This is the first report on the study of a human antibody against CAMP1 of C. acnes phylotype II, of which a potential use as therapeutic antibody against virulence C. acnes infection is postulated.

Recently, JAKi has also been widely proved to be an effective alternative to conventional treatment for Synovitis acne pustulosis-hyperostosis-osteitis (SAPHO) cases, after failure of multiple drugs including those described above. But what to do when all these treatments fail? We report a case of remission from Tripterygium wilfordii Hook (TwHF) treatment.

The patient was treated with nonsteroidal anti-inflammatory drugs, oral prednisone, minocycline, bisphosphonate injection, etanercept, and tofacitinib, but the symptoms did not change significantly. Treatment with TwHF (1.0 mg/kg/day, patient weight 60 kg) was started for 24 weeks.

After 50 months of unsatisfactory treatment, this patient was finally treated with herbal TwHF, and after 6 months of treatment, the patient's magnetic resonance imaging and inflammatory indexes were significantly improved, indicating that the disease had been better controlled.

In this study, TwHF was successful in treating a patient with refractory SAPHO syndrome who was refractory to multiple Western medications without significant adverse effects or toxicities, but further follow-up is needed to determine long-term efficacy. More case reports as well as clinical trials are still needed to confirm whether TwHF can effectively treat refractory SAPHO syndrome.

This study aimed to analyse the radiological characteristics and clinical diversity of Japanese patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a heterogeneous disorder.

Radiographs and clinical information from 115 Japanese patients (female/male: 81/34; mean age at onset: 48.7 years) diagnosed with SAPHO syndrome between January 2007 and December 2020 were retrospectively reviewed. Additionally, the treatment for SAPHO syndrome was explored.

Among the 115 patients, 70 patients had complications, including palmoplantar pustulosis, acne, or psoriasis. Imaging studies included bone scintigraphy, magnetic resonance imaging, computed tomography, and positron emission tomography in 71, 58, 70, and 23 patients, respectively. The most frequent lesions were arthritis and hyperostosis of the sternoclavicular joints in 96 patients; spinal lesions, including sacroiliac arthritis, were observed in 85 patients. Peripheral aseptic osteitis was observed in 22 patients, and the tibia was involved in 12. The treatments consisted of analgesics, bisphosphonates, conventional synthetic disease-modifying antirheumatic drugs, and biologics (tumour necrosis factor inhibitors and interleukin-23p19 inhibitors) in 85, 15, 23, and 10 patients (8 and 2 patients), respectively.

Sternoclavicular hyperostosis and pustulosis are frequently observed in patients with SAPHO syndrome. Biological agents were more frequently used in patients with peripheral osteitis and arthritis.

Considered rare, the synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome is a distinct clinical entity, associating skin manifestations and osteoarticular symptoms. Anterior chest wall pain centered at sternoclavicular and sternocostal joints is an important and characteristic clinical finding that can lead to its diagnosis. Radiologists and clinicians must be aware of synovitis-acne-pustulosis-hyperostosis-osteitis syndrome as it can mimic some of the more common disease entities such as Paget's disease. We report the case of a 63-year-old male patient, with no significant medical history, who presented to the dermatology department, with severe palmar and plantar pustulosis associated with polyarthralgia. Computerized tomography scan showed sternoclavicular hyperostosis, in favor of SAPHO syndrome, with regression of clinical symptoms after non-steroidal anti-inflammatory drug treatment.

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.

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.

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.

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.

SAPHO syndrome is a complex disease that encompasses both inflammatory arthritis and/or osteitis and dermatologic manifestations. It is considered a rare disease, in fact, no clinical trials have been conducted on its therapy and management. Therefore, therapeutic approach is based on small case studies. Here, we described the case of a 63-year-old woman affected by SAPHO syndrome, treated with the selective IL-23p19 antagonist, Risankizumab, after unsuccessful therapies with Methotrexate, Infliximab, Adalimumab, and an allergic reaction to Secukinumab. At the beginning of therapy, in November 2022, the patient presented with arthritis in both knees associated with palmar pustulosis and guttate psoriasis on the trunk. DAPSA score was 24, PtGA 80 mm, PASI score 11.1, and BSA 40%. Thereafter, Risankizumab was started at the standard dosage of 150 mg. At week 24 patient achieved clinical remission, DAPSA score was 8, PtGA was 30 mm, PASI was 1, and BSA 2.5. Patient maintained clinical remission state at the subsequent week 52 evaluation. At the same time, the patient did not report any adverse effects. Health-related quality of life was also assessed at the same time points aforementioned, showing significant improvement. In conclusion, this case report wants to point out the efficacy and safety of Risankizumab in SAPHO syndrome, reporting a sustained disease remission through a 12 months long follow-up period. We can consider IL-23p19 targeted therapy as a novel treatment option for SAPHO-with a high efficacy potential-especially on patients that have already been treated with other biologics.

Chronic nonbacterial osteitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride-18 positron emission tomography/computed tomography ([18F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluated the capacities of [18F]NaF-PET/CT to provide structural and functional assessment in adult CNO. A coss-sectional study was performed including 43 adult patients with CNO and 16 controls (patients referred for suspected, but not diagnosed with CNO) who underwent [18F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values (SUVmax [g/mL]) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUVmax was correlated with clinical disease activity in patients. Structural assessment revealed manubrial and costal sclerosis/hyperostosis and calcification of the costoclavicular ligament as typical features associated with CNO. SUVmax of CNO lesions was higher compared with in-patient reference bone (mean paired difference: 11.4; 95% CI: 9.4-13.5; p < .001) and controls (mean difference: 12.4; 95%CI: 9.1-15.8; p < .001). The highest SUVmax values were found in soft tissue and joint areas such as the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient: 0.546; p < .002). Our data suggest that [18F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue, and joint features. At the same time, [18F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision making.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune disease characterized by skin or osteoarticular damage. SAPHO syndrome is often misdiagnosed or missed diagnosis due to lack of overall understanding of the disease by clinicians.

To analyze the clinical symptoms and imaging features of six Han patients with SAPHO syndrome in order to provide reference for doctors to diagnose SAPHO syndrome.

This study retrospectively analyzed the clinical data of six Han patients with SAPHO syndrome.

All six Han patients with SAPHO syndrome had severe acne or pustulosis of the hands and feet, and all of them had osteoarticular damage, including five cases involving the sternoclavicular joint. Some patients showed a specific and typical "bull's head" sign on 99mTc-labeled methylene diphosphonate bone imaging. Among the six patients recruited, there was one thoracic vertebra, one cervical vertebra, one sacroiliac joint, and one peripheral joint involvement. Two patients had limited activity due to severe osteoarticular damage.

Due to the atypical clinical symptoms of SAPHO syndrome, most patients will experience a tortuous and long diagnostic process, while a correct understanding and timely intervention of SAPHO syndrome are essential to improve the prognosis of patients.

We aimed to analyze the clinical characteristics and outcomes of patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

The clinical records of 64 patients with SAPHO syndrome were collected, and the treatment and outcomes of 27 patients were followed up. The patients were divided into three groups according to the site of bone lesions: only anterior chest wall (ACW) involvement, only spinal involvement, and bone lesion involvement at both sites. The clinical characteristics and outcomes were compared. The clinical characteristics of the patients with and without peripheral joint involvement were compared.

Among all patients, 31.25% (20/64) had only ACW involvement, 15.63% (10/64) had only spinal involvement, and 53.12% (34/64) had both ACW and spinal involvement. Peripheral joint involvement was observed in 25.00% (16/64) of the patients. Patients with only spinal involvement were older than those with only ACW involvement (p = 0.006). Patients with both ACW and spinal involvement were older than those with only ACW involvement (p = 0.002) and had a longer diagnosis delay (p = 0.015). Patients with peripheral joint involvement were younger than those without peripheral joint involvement (p = 0.028). During follow-up, 88.89% (24/27) of patients had good outcomes. Twenty-two patients were treated with non-steroidal anti-inflammatory drugs + Iguratimod (IGU), and the outcomes of 90.91% (20/22) improved.

A relationship may exist between the sites of bone lesions and clinical characteristics of patients with SAPHO syndrome. The clinical outcomes of these patients may be good, and IGU may be effective in treating SAPHO syndrome. Key Points • This study is the first long-term follow-up on the effectiveness of iguratimod in treating patients with SAPHO. • This study revealed that patients with SAPHO and different bone lesion sites may present with different clinical characteristics.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is a rare chronic inflammatory disease that develops in adults. We present a case of SAPHO syndrome in a 37-year-old male presenting with gradually worsening back and neck pain for a 7-year period. The episodes were preceded by a history of pustular skin eruptions, which first appeared on the upper trunk and then involved his face and were pustular and scarring. The purpose of presenting this case report from Iraq is to raise awareness about this rare condition, which is frequently misdiagnosed and under-recognized.

Acne is a common skin disorder in adolescents. However, severe acne that is persistent and refractory to conventional treatment or has other associated symptoms should raise suspicion for non-syndromic or syndromic acne.

Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features. CNO pathophysiology, including the key drivers of inflammation, remains largely unknown. For pediatric CNO, a role for pro-inflammatory cytokine dysregulation has been proposed, but studies in adults are scarce. We therefore provide immunological characterization of adult CNO. Cross-sectional study in our referral center including adult CNO patients (n = 172) and healthy controls (n = 65). Inflammation parameters and systemic inflammatory based scores(SIBS, including neutrophil/lymphocyte ratio [NLR] and systemic immune inflammation index [SII]) were compared between groups. Cytokine expression was explored with electrochemiluminescent immunoassays in 33 patients, eight healthy controls and 21 osteoporosis patients. Routine inflammation markers were higher in patients than in controls, but generally remained within reference range. Systemic inflammation was more pronounced in patients with additional vertebral involvement as compared to those osteitis in the anterior chest wall alone, in patients with comorbid pustulosis palmoplantaris or psoriasis, and in patients with strongly rather than moderately increased lesional uptake on nuclear imaging. SII was elevated in CNO patients too, but NLR was not. Cytokine expression was generally nondifferential between patients and both control groups, and patients displayed low absolute concentrations of pro-inflammatory cytokines. In this adult CNO cohort, systemic inflammation was generally subtle, but more pronounced in patients with vertebral lesions, associated skin disease, and strongly increased uptake on nuclear imaging. SII was increased in patients compared to healthy controls. Contrasting pediatric studies, we found no increased expression of the pro-inflammatory cytokines that have been proposed to drive the inflammatory cascade, like interleukin-6, -8, and -17 (IL-6, IL-8, and IL-17), and tumor necrosis α (TNF-α). Further studies are needed to evaluate the use of SII in diagnosis and monitoring of CNO, and elucidate the role of cytokine dysregulation in adult disease. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune inflammatory disease characterized by osteoarticular and dermatological manifestations. The most common osteoarticular manifestations involve the anterior chest wall, axial skeleton, and long bones. Cranial bone involvement is less reported in SAPHO syndrome. We herein present three cases of SAPHO syndrome with cranial bone involvement, and review the previous literature on similar manifestations. It was revealed that SAPHO syndrome could lead to cranial bone involvement, which could involve the dura mater, leading to hypertrophic pachymeningitis, but the outcome is usually good. Janus kinase inhibitors may be a potential treatment option.

SAPHO (Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis) syndrome is a heterogeneous disease that clinically manifests as chronic inflammatory osteoarticular and dermatological lesions. Few reports have described familial clustering of SAPHO syndrome cases. This research aimed to illustrate the family aggregation of SAPHO syndrome and investigate the prevalence of autoimmune disorders among SAPHO syndrome patients and first-degree relatives in a large cohort.

We retrospectively reviewed the medical records of 233 SAPHO patients diagnosed at Peking Union Medical College Hospital. Direct phone calls were made to each first-degree relatives. All relatives of the patients who reported SAPHO syndrome were asked for a detailed outpatient evaluation.

A total of 233 patients and 1227 first-degree relatives were recruited. Six (2.6 %) patients had positive SAPHO family history, including four mother-daughter pairs and two sister pairs. Twenty-one (9.0 %) patients presented at least one kind of autoimmune disease, including 12 rheumatoid arthritis and 4 ulcerative colitis cases. Fifty-eight (24.9 %) SAPHO syndrome patients had 68 (5.5 %) first-degree relatives with at least one autoimmune disorder. The palmoplantar pustulosis, psoriasis vulgaris, and rheumatoid arthritis prevalence in our subjects were each higher than reference rates.

This is the first evaluation of familial aggregation for SAPHO syndrome in a large cohort. SAPHO syndrome has a weak familial aggregation. There is a relatively high prevalence of coexisting autoimmune disease among patients with SAPHO syndrome and their first-degree relatives. These results would prompt physicians to screen SAPHO syndrome patients and their family members for concomitant autoimmune diseases.

This study suggesting a potential genetic component in the pathogenesis of SAPHO syndrome. This study is the first to evaluate the family aggregation of SAPHO syndrome in a large cohort.

A 79-year-old man presented with fatigue and right shoulder pain. Computed tomography revealed right pleural effusion and osteosclerosis of the sternoclavicular joint. There were no signs of malignancy or infection in the pleural fluid studies. His bone scintigraphy exhibited the "bull's head sign." Despite the absence of skin lesions, he was diagnosed with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome. Remission was achieved after treatment with non-steroidal anti-inflammatory drugs and oral prednisolone. SAPHO syndrome causes pleural effusion, even in patients without skin lesions. Bone scintigraphy should be considered in the workup for patients with unexplained pleural effusion.

Early diagnosis of SAPHO syndrome is easily confused with other common spine-related diseases and infections. There is currently no consensus regarding the diagnosis of SAPHO syndrome, and specific treatments are empirical because of its rarity.

A 62-year-old woman was referred to our department with complaints of low back and lower extremity pain for 2 years, 1.5 years after lumbar spine surgery, and recurrent low back pain for 1 year. Laboratory test results revealed elevated hs-CRP levels and erythrocyte sedimentation rate. Combined with her surgical history and lumbar CT results, adjacent segment degeneration (ASD) was first considered. NSAIDs, analgesics, and supplemental therapies were also administered. However, the patient's symptoms were not significantly relieved. During re-examination, hyperkeratosis with active pustulosis was observed on the patient's palms. Osteitis of the left sacroiliac joint was revealed on imaging. Skeletal ECT revealed a typical "horn sign". The patient was diagnosed with SAPHO syndrome. Based on the original treatment, sulfasalazine enteric-coated tablets, adalimumab (a biological agent of TNF-α), pregabalin, and tramadol sustained-release tablets were administered. The patient reported that her pain was significantly relieved. He was discharged from the hospital and received adalimumab treatment (40 mg once per fortnight in the first 6 months and 40 mg once per month after month 6) in the outpatient clinic. The hyperkeratosis with active pustulosis on both palms fully recovered after 12 months of treatment. The patient was followed up 6 months after full recovery, and no recurrence was found in the symptoms of low back and lower extremity pain and palmar hyperkeratosis with active pustulosis.

SAPHO syndrome should be suspected in patients present with osteoarticular and/or dermatological manifestations. Biological agents can be used to treat patients with refractory SAPHO syndrome.

Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.

A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.

36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments.

Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.

Autoinflammatory bone disorders are a group of diseases characterized by sterile osteomyelitis. This includes chronic nonbacterial osteomyelitis and the monogenic forms, Majeed syndrome and deficiency of the interleukin-1 receptor antagonist. These disorders result from innate immune system dysregulation and cytokine imbalance that triggers inflammasome activation causing downstream osteoclastogenesis and excessive bone remodeling. In this review, we will summarize the immunopathogenesis of pediatric autoinflammatory bone diseases with a special focus on the genetics and inborn errors of immunity, while briefly touching on the clinical manifestations and management of each disease as well as areas for future research.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) is a relatively rare and often underdiagnosed disorder characterized by chronic inflammation affecting the bones, joints, and skin. While the precise cause of SAPHO syndrome remains elusive, multiple factors such as genetics, immunological dysregulation, and bacterial influences have been implicated in its pathogenesis. One notable aspect of SAPHO syndrome is the wide variability of symptoms experienced by afflicted individuals. A diverse array of osteoarticular manifestations may be observed, with common sites of involvement including the anterior chest wall, sacroiliac joints, and peripheral joints. Concurrently, patients often present with various skin disorders, such as palmoplantar pustulosis or acne, further adding to the complexity of the syndrome's clinical presentation. Treatment strategies for SAPHO syndrome primarily focus on managing symptoms and improving the quality of life for affected individuals. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, methotrexate (MTX), and tumor necrosis factor (TNF) inhibitors are considered to modulate the immune response and provide relief. One of the challenges encountered in diagnosing SAPHO syndrome is its potential overlap with other related conditions, leading to diagnostic confusion and difficulties. Distinguishing SAPHO syndrome from similar entities can be complex, requiring a comprehensive evaluation of clinical features, imaging studies, and laboratory investigations. We would like to share an intriguing case involving a 28-year-old woman who arrived with perplexing symptoms of pain in her bilateral hands and feet, her lower back, and acne in the bilateral upper arms and thighs. Through a comprehensive workup, the underlying SAPHO syndrome was uncovered, and it was effectively managed using adalimumab.

Synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome is a rare musculoskeletal disease characterized by dermatological and osteoarticular lesions. However, SAPHO syndrome is difficult to be diagnosed due to the rarity and complexity. Additionally, there is no standard treatment for SAPHO syndrome based on limited experience. Percutaneous vertebroplasty (PVP) has rarely been reported to treat SAPHO syndrome. We reported a 52-year-old female patient who had a sex-month history of back pain. Palmoplantar pustulosis appeared on the hands and feet. Vertebral destruction was observed on computed tomography (CT) scanning. Laboratory examination showed that erythrocyte sedimentation rate (ESR) and C-reactive protein were elevated. Finally, the patient was diagnosed with SAPHO syndrome and treated with PVP. After the surgery, the back pain was significantly relieved. In this study, we mainly discussed the treatment methods of SAPHO syndrome, and provided a potential treatment for SAPHO syndrome, especially with vertebral destruction, kyphosis, and even pathological fractures.

Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus.

Systematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI.

Forty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively.

CNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare autoinflammatory condition describing the constellation of inflammatory skin, bone, and joint manifestations which result in diagnostic difficulty and therapeutic challenge.

Here, we present a case of a young male diagnosed with SAPHO syndrome with osteoarticular and cutaneous involvement from an early age in his life. He suffered diagnostic challenges for a long time and was hence inadequately treated. He had minimal response to conventional DMARDs but showed excellent response to TNF inhibitor (adalimumab). Later, he defaulted treatment and presented with acute anterior uveitis which was also dramatically improved with adalimumab and tofacitinib although financial constraint was always an issue for the patient.

The uniqueness of this case was that the patient had a multiorgan involvement including osteoarticular system, skin, and eye. Both TNFi (adalimumab) and JAKinib (tofacitinib) had a good response to all organs with a net improvement in the quality of life of this patient.

We report a case of isolated lesions of the thoracic spine attributed to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A 55-year-old woman who suffered from 6 months of back pain had vertebral osteomyelitis on magnetic resonance imaging (MRI). There were no laboratory findings suggestive of infection, malignancy, or autoimmune disease. Radiography, computed tomography (CT), and MRI of the thoracic spine showed mixed lesions of sclerosis and erosion, whereas bone scintigraphy did not show accumulation at any site except the thoracic spine. No lesions in the anterior chest wall or sacroiliac joints were apparent from CT and MRI. No lesions other than at the thoracic spine were observed. As the isolated lesions of the thoracic spine were considered not to have resulted from infection, malignancy, or autoimmune disease, the patient was referred to our department for differential diagnosis. Given that isolated sterile hyperostosis/osteitis among adults is included in the modified diagnostic criteria for SAPHO syndrome, we suspected that the mixed lesions of sclerosis and erosion of the thoracic spine in this case may reflect SAPHO syndrome with chronic non-bacterial osteitis (CNO) of the thoracic spine. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated and led to alleviation of her back pain, although the thoracic spine lesions remained on the 6-month MRI. Based on the CNO of the thoracic spine and the rapid response to NSAIDs, the final diagnosis was SAPHO syndrome with isolated lesions of the thoracic spine.

SAPHO is an acronym derived from capital letters of Synovitis, Acne, Pustulosis, Hyperostosis, and Osteitis (SAPHO). SAPHO syndrome is an umbrella term covering a constellation of bone lesions and skin manifestations. A 40-year-old male complained about his jaw and back pain, swelling of multiple joints and weight loss accompanied by physical deterioration and acne type skin lesions. Laboratory tests revealed abnormal elevation of inflammatory markers. Imaging studies illustrated multiple osteolytic bone lesions and paraosseal infiltrates. According to the set of criteria diagnosis of SAPHO syndrome was stated. The patient was treated with glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs), but only high dose dexamethasone and prednisone were effective. Daily subcutaneous administration of anakinra at the dose of 100 mg was initiated due to limited response to more classical therapies. Because of planned mandibular osteosynthesis initiation of denosumab was preferred before bisphosphonates. Therapeutic response was confirmed by FDG-PET/MR after 5 months of anakinra and denosumab therapy, showing decreased accumulation of FDG in periosteal and paraosseal infiltrates. Inflammatory markers significantly decreased, bone pain deferred but skin manifestation receded only partially. Therefore the response was evaluated as partial remission.

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic inflammatory disease with osteoarticular and cutaneous involvements as its main manifestations. Acne conglobata as a severe acne form may affect adolescent patients. Tumor necrosis factor inhibitors are usually used as a second-line therapy for refractory SAPHO syndrome and has been reported to treat acne conglobata successfully. We herein report three cases of adolescent patients with SAPHO syndrome associated with acne conglobata who were successfully treated with TNFi therapy.