7-year old female develops inflamed well demarcated annular patches with golden crust on the plantar surface of both feet. Treated initially for infected discoid eczema in the community. Unresponsive to topical corticosteroids and oral antibiotics. Patient then developed acute left sided lower limb (LLL) bone pain with no pyrexia and a c-reactive protein of 9. MRI imaging showed multiple sites of osteomyelitis in the LLL. Histology from bone aspirate was normal and gram stain/culture was negative. Case was reviewed by rheumatology/paediatric team at tertiary centre, and a diagnosis of SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) and CRMO (chronic recurrent multifocal osteomyelitis) was established. She commenced NSAIDs and Anti-TNFa biologic. 12 weeks into treatment the bone pain improved however, the patient developed paradoxical psoriasis on head, neck and limbs. Therapy was switched to IL-17A inhibitor with amelioration of paradoxical psoriasis and improvement seen in inflammatory patches on the plantar aspect of feet after 4 weeks. The prevalence of CRMO in the paediatric population is approximately 0.4/100 000 with a female preponderance. There are case reports in adult patients with SAPHO syndrome developing paradoxical psoriasis after adalimumab, with case series demonstrating improvement in palmoplantar pustulosis after secukinumab. More evidence is required to establish the efficacy of IL-17A inhibitors in the treatment of SAPHO in the paediatric age group. We present a patient with a rare case of SAPHO and CRMO with worsening cutaneous symptoms after commencing anti-TNFa. This paradoxical reaction cleared rapidly on switching to secukinumab (IL-17A inhibitor).

Still's disease (SD) is a rare systemic inflammatory disorder of unknown origin, characterized by episodes of uncontrolled inflammation. While natural killer (NK) cells have been implicated in SD pathogenesis, their precise role remains elusive. Within the framework of the ImmunAID consortium, we performed a comprehensive NK cell phenotyping in an international cohort comprising 121 patients with distinct systemic autoinflammatory diseases (53 SD, 23 chronic recurrent multifocal osteomyelitis, 23 Familial Mediterranean fever, and 22 inflammation of unknown origin) and 32 healthy controls. Our analysis revealed a unique NK cell signature in SD, characterized by a reduction in NK cell frequency and elevated Fas expression, rendering them more susceptible to in vitro Fas ligand-induced apoptosis. Fas ligand was expressed by SD monocytes and CD38+HLA-DR+ cycling lymphocytes. SD NK cells displayed a hyperactivated but exhausted phenotype, including cytokine unresponsiveness, all features not observed in the other groups. This NK cell dysfunctional profile normalized during clinical remission. Exposure of healthy NK cells to IL-12, IL-15 and IL-18 recapitulates the SD-associated phenotype, suggesting an inflammation-driven mechanism. Transcriptomic profiling identified microRNA miR-146a as a potential regulator of this NK cell dysfunction. Our findings establish NK cell apoptosis, exhaustion, and cytokine unresponsiveness as defining immunological features of SD, distinguishing it from other inflammatory diseases in this cohort. This dysfunctional NK cell state may underlie the heightened risk of macrophage activation syndrome in SD and highlights inflammatory cytokines and miR-146a as promising therapeutic targets to mitigate disease severity and prevent life-threatening complications.

Caffey’s disease, first described by Caffey and Silverman in 1945 is also known as infantile cortical hyperostosis (ICH), is a condition that affects infants and is mostly self-limiting. Presenting with painful soft tissue swellings, fever and irritability, it is characterized by cortical thickening of the underlying bones. Its clinical presentation can mimic infectious osteomyelitis, leading to diagnostic challenges. We report a case of a 2-month-old male infant with multifocal bony involvement and genetic findings suggestive of chronic recurrent multifocal osteomyelitis (CRMO), but with clinical features strongly favouring Caffey disease. This case highlights the overlap between autoinflammatory bone disorders in infancy and emphasizes the importance of integrating clinical, radiological, and genetic findings to arrive at an accurate diagnosis. This case is reported to get the awareness of the paediatricians about the disease, its existence in our population, presentation, and important differential diagnoses and management.

Abstract Introduction Chronic recurrent multifocal osteomyelitis (CRMO) is a sterile, autoinflammatory condition of bone that affects children and adolescents and presents with bone pain, bony tenderness or swelling. It can be associated with other inflammatory conditions including inflammatory bowel disease, Takayasu’s arteritis, palmo-pustular psoriasis, acne, pyoderma gangrenosum, sweet syndrome and sclerosing cholangitis to name a few. The importance of this is to consider these other conditions when a patient has symptoms suggestive of those with a background of CRMO, or the other way round. Case description Our patient was a 11-year-old boy at presentation, had been previously fit and well with unknown family history as he was adopted. He presented to paediatrics with right sided hip pain which had begun to limit his physical activity and inconsistent history of night pain. He was pale with restriction of movements of right hip and forward flexion of spine with tight hamstrings and no other significant physical findings. He had an MRI pelvis after discussion with orthopaedics, and this showed bone marrow oedema of bilateral neck of femur, greater trochanter and right acetabulum. He was felt to have CRMO at this point and seen by paediatric rheumatology. His blood investigations showed mildly raised inflammatory markers with normal counts. His whole body MRI showed bone marrow oedema of T12-L2, in addition to above changes. His symptoms were cyclical lasting 3-4 weeks, often affecting ribs, back, right hip and thigh. It improved with regular anti-inflammatory agents but never completely went away. His inflammatory markers were creeping up with ESR 54 and CRP 37. His blood counts, vitamin D and bone profile were normal. Given his spinal lesions and ongoing symptoms, he was discussed at the radiology MDT and given bisphosphonate infusions. Hardly a month later, the pain resurfaced and was worse, he was fatigued and had night time pain, more over the chest and back. His blood investigations remained the same with raised inflammatory markers. He had further imaging both MRI spine and whole-body MRI. At this point, the greatest concern was malignancy. He was discussed with haematology and had a bone marrow biopsy that was normal. He had a pulse of IV methylprednisolone after discussions with oncology who felt strongly this wasn’t malignancy. This helped transiently for 2 months before things took a turn for the worse. Discussion A year after his first presentation, this boy was still symptomatic, fatigued, had lost weight, 3 kgs in 3 months, developed night sweats and looked pale. His inflammatory markers had never reached baseline throughout, and he had refrained from most physical activities. His blood investigations showed dropping Hb 106 , rising platelets 604, rising CRP 99 and ESR 87 with normal white cells. Our team felt strongly about malignancy and pushed for CT chest abdomen and pelvis as per oncology protocol. This revealed diffuse irregular dilatation of the aorta with aneurysmal dilatation of left proximal subclavian artery. This was suggestive of Takayasu’s arteritis. We discussed this patient at the national vasculitis consortium. He was pulsed with IV methylprednisolone with weaning oral steroids and had 5 cycles of cyclophosphamide. His symptoms improved, gained weight, and energy levels improved, and he went back to his activities. He was then commenced on methotrexate and anti TNF for maintenance and is doing well currently. It was important that we had kept questioning the diagnosis given that his symptoms and inflammatory markers never settled and pushed for further investigations to uncover his entire diagnosis. It is hard to say if his CRMO presented first with Takayasu’s as an association or his musculoskeletal symptoms were a veiled presentation of Takayasu’s arteritis. Key learning points Persistent systemic symptoms or inflammation in CRMO is unusual, look for alternative diagnosis especially malignancy and associations with CRMO including Inflammatory bowel disease and vasculitis. In any clinical scenario if despite treatment plans carried out, the patient is not improving back to baseline, or the family are concerned, reconsider the diagnosis. When reviewing patients with CRMO, keep in mind associations and ask specific history considering those as well as focussed examination, and investigations including faecal calprotectin, HLA B27, radiological imaging as needed. Role of multidisciplinary team discussions are invaluable including radiology, oncology and allied health professionals amongst others.

BACKGROUNDChronic recurrent multifocal osteomyelitis (CRMO) is a rare autoinflammatory bone disorder primarily affecting children and adolescents. Spinal involvement in CRMO is common and can lead to significant clinical features and complications, including severe chronic back pain and spinal deformities with possible spinal cord compression.AIMTo summarize the information about vertebral involvement in CRMO patients, including the clinical features, diagnostic approaches, and treatment outcomes.METHODSSixty-three manuscripts (2005-2025) were found in PubMed, including case reports, retrospective cohort studies, randomized controlled trials, and imaging studies. The focus was on spinal involvement features, diagnostic imaging, treatment strategies, and long-term outcomes in pediatric CRMO patients.RESULTSSpinal involvement in CRMO ranges from 28% to 81% among patients with CRMO. Patients typically present with localized back pain, back stiffness, and, in more severe cases, spinal deformities such as kyphosis or scoliosis. Multifocal lesions are frequently observed, with the thoracic spine being the most commonly affected area. Whole-body magnetic resonance imaging (WBMRI) has emerged as the gold standard for effectively revealing multifocal bone lesions and spinal involvement. However, a bone biopsy is often needed to rule out infection or malignancy. Bisphosphonate treatment showed a high response rate (90.9%), while tumor necrosis factor-alpha (TNF-α) inhibitors were less effective (66.7%). Long-term follow-up is crucial, as relapses and progression of spinal deformities can occur even with treatment.CONCLUSIONSpinal involvement in CRMO often leads to chronic pain, vertebral deformities, and rare spinal deformities. Early diagnosis using WBMRI, combined with treatment with bisphosphonates and TNF-α inhibitors, could improve outcomes.

An Indian girl, diagnosed with osteoid osteoma of tibia and chronic recurrent multifocal osteomyelitis at the age of 6 years, presented 3 years later with slipped capital femoral epiphysis (SCFE) and was found to have a mutation in the GALNT3 gene associated with hyperphosphatemic familial tumoral calcinosis. She underwent in situ screw fixation with prophylactic pinning of the other hip. At a 2-year follow-up, the patient had a good range of motion and no radiological signs of osteonecrosis of the femoral head. GALNT3 gene mutation with SCFE is a previously unreported association, emphasizing the need for a multidisciplinary approach.

Tyrosine kinase 2 (TYK2) mediates the signaling pathways of proinflammatory cytokines such as interleukin (IL)-12, IL-23, and type I interferons (IFNs) and plays a pivotal role in the pathogenesis of psoriasis and various other immune-mediated diseases. Deucravacitinib, a selective oral TYK2 inhibitor, has been approved for the treatment of psoriasis and demonstrated high efficacy and a favorable safety profile. This review summarizes the potential for expanding deucravacitinib indications based on case reports, clinical trials, and preclinical studies. Diseases in which TYK2 pathway has been demonstrated to be involved and for which clinical benefit of deucravacitinib has been reported include discoid lupus erythematosus, systemic lupus erythematosus, alopecia areata, lichen planus, palmoplantar pustulosis, psoriatic arthritis, systemic sclerosis, interstitial pneumonia, inflammatory bowel disease, and chronic recurrent multifocal osteomyelitis. Furthermore, emerging research suggests potential therapeutic applications in neurodegenerative diseases such as Alzheimer's disease, and malignancies such as type 1 diabetes, vascular calcification in chronic kidney disease, T-cell acute lymphoblastic leukemia, and multiple sclerosis. Deucravacitinib may exert therapeutic effects by broadly suppressing cytokine signaling in a diverse range of inflammatory disorders. Ongoing clinical trials and mechanistic studies are required to clarify the efficacy and support its future indications.

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare auto-inflammatory condition affecting the growing skeleton. The standard first-line treatment of high-dose NSAIDs (non-steroidal anti-inflammatory drugs) is adequate only in a subset of patients. The American College of Rheumatology Consensus Guidelines suggest considering bisphosphonates in a certain category of patients based on evidence from a handful of case series reporting the outcome of pamidronate use. Aims: The aim of this study was to report the efficacy and safety of bisphosphonate, predominantly zoledronate, use in CRMO. Methods: A retrospective cohort study of children with CRMO receiving bisphosphonates was conducted between January 2008 and September 2023 at a single tertiary referral centre. We described the baseline characteristics; clinical indication, regimen and response to bisphosphonate treatment; changes in bone mineral density (BMD) and spine remodelling on dual-energy X-ray absorptiometry (DXA) scans; and safety data. Results: During the study period, 64 (72%, n = 46 females) patients with CRMO with a median age at diagnosis of 10 years (range: 3 to 16 years) were identified. Approximately 31% (n = 20) received either pamidronate (n = 2) or zoledronate (n = 14) or both (n = 4) due to changes in local protocols. The most frequent indications for bisphosphonate use were refractory pain [55%, n = 11/20], pain + spine involvement [35% (n = 7/20)] and spine involvement only [10% (n = 2)]. Prior to bisphosphonate therapy, 100% took regular NSAIDs (n = 19/19), 21% (n = 4/19) used opioids, 47% (n = 9/19) received oral steroid courses, and 10% (n = 2/19) received methotrexate. The median age at bisphosphonate treatment initiation was 12 years (range 6–18 years), and the duration of treatment was 2 years (range: 6 months to 5 years). Improvement in pain was reported by 88% of patients (n= 15/17, 1 was excluded as they had not started treatment yet). All non-responders (n = 2/17;) to bisphosphonate therapy were later recognised clinically to have pain amplification syndrome and were referred to the chronic pain multi-disciplinary team. This correlated to the complete treatment de-escalation of opioids (n = 3/3; 1 was excluded as they had not yet started treatment), steroids (n = 8/8) and methotrexate (n = 2/2). NSAIDs were discontinued in 44% of patients (n = 7 of 16; 1 was excluded due to missing data, and 3 were excluded due to NSAID intolerance). The median first-year increase in the LS BMAD (lumbar spine bone mineral apparent density) Z-score was +1.35, and that in the TBLH BMD (total body less head bone mineral density) Z-score was +0.7 (n = 11). Subsequently, median average annual increases in the LS BMAD Z-score of +0.65 and in the TBLH BMD Z-score of +0.45 (n = 5) were recorded. Around 30% of patients (n = 6) required treatment modification (dose reduction, frequency reduction or cessation) due to a rapid escalation in BMD. There were no fractures documented due to raised BMD. Evidence of spine remodelling on DXA vertebral fracture assessment was seen in 38% of patients with spinal lesions (n = 3 of 8). There was no radiological evidence of improvement in any vertebra plana lesion. First-phase reactions (pyrexia) were reported universally in patients who received bisphosphonates, but none were significant requiring hospitalisation. Conclusions: Similar to pamidronate, zoledronate with an advantageous dosing regimen is well tolerated and effective in improving pain and enabling the de-escalation of adjunctive therapy in CRMO. This is the first report tracking changes in BMD and spinal remodelling in response to zoledronate in CRMO patients. Spinal remodelling is minimal in vertebra plana lesions. Bone density monitoring and personalisation of the bisphosphonate dose and regimen are strongly recommended to avoid overtreatment.

BackgroundThis multicenter study aimed to address the heterogeneity of chronic recurrent multifocal osteomyelitis (CRMO) by identifying clinical subtypes through cluster analysis, exploring clinical features, treatment approaches, and short-term prognosis to improve management of pediatric CRMO.MethodsData from 42 pediatric CRMO patients (47.6% male; mean age 7.87 ± 3.45 years) diagnosed between June 2018 and June 2024 were analyzed. Using cluster analysis with 17 variables, patients were categorized into phenotypic subgroups. Statistical tests assessed differences in clinical features, treatment, and outcomes. Kaplan-Meier survival analysis and log-rank tests evaluated recurrence risk and final Physician Global Assessment(PGA) scores.ResultsPatients were classified into two groups: chronic bone pain and acute systemic inflammation. Significant differences were found in fever occurrence (P = 0.002), C-reactive protein (CRP), interleukin-6(IL-6), cytokines including tumor necrosis factor-α(TNF-α) elevation (P = 0.013, 0.003, 0.029), and Hemoglobin(HB), alkaline phosphatase (ALP) reduction (P = 0.007, < 0.001). PGA scores also differed significantly (P < 0.001). Although baseline differences existed, post-treatment recurrence risk and final PGA scores showed no significant differences (P = 0.247, P = 0.211). Treatment differed only in glucocorticoid use; non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs(DMARDs), TNF inhibitors, and diphosphonates showed no statistical differences. Both groups reached remission approximately 12 months post-diagnosis.ConclusionTwo distinct clinical phenotypes of pediatric CRMO were identified, each achieving favorable outcomes with tailored treatments. Recognizing these phenotypes may guide clinical strategies and improve prognosis for CRMO patients.

BACKGROUND: Currently, there is no etiological treatment for chronic nonbacterial osteomyelitis. The insufficient efficacy of all available treatment modalities remains a major concern. Among the most effective approaches are genetically engineered therapy and bisphosphonate treatment. Pamidronate is the most frequently reported option in scientific publications. However, given pamidronates’ lower efficacy compared to zoledronic acid, we developed a treatment protocol that includes zoledronic acid at a dose of 0.05 mg/kg every 3 months, three infusions in total, along with active vitamin D metabolites and calcium carbonate. AIM: This study aimed to demonstrate the efficacy of zoledronic acid in the treatment of chronic nonbacterial osteomyelitis. METHODS: The study included 22 children aged 6 to 17 years. A prospective pilot study was conducted to assess the efficacy of zoledronic acid in children with chronic recurrent multifocal osteomyelitis. All patients underwent biopsy with morphological and microbiological verification of the diagnosis, as well as laboratory and imaging assessments before and 3, 6, and 12 months after treatment. Clinical disease activity was assessed using a visual analog scale for pain and the PedsQL 4.0 quality of life questionnaire. RESULTS: Preliminary treatment outcomes in patients receiving this regimen are promising. Pain was significantly reduced, quality of life improved, and the number of bone lesions decreased, with clinical remission achieved in all patients. CONCLUSION: Zoledronic acid rapidly inhibits osteoclast activity, leading to both clinical and radiological remission, as evidenced by decreased pain, reduction of bone marrow edema on MRI, and sclerosis of lytic lesions. Given the reduced osteoclast activity in the post-injection period, this therapy must be combined with active vitamin D metabolites and calcium carbonate to maintain calcium-phosphorus homeostasis.

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is a sporadic form of autoinflammatory bone disorders (ABDs) presenting with sterile chronic and/or recurrent and multiple sites of bone involvement. We aimed to describe our 10-year cohort of CRMO patients and analyze the characteristics and treatment approaches.MethodsWe retrospectively analyzed the data on patients with bone diseases at Children’s Medical Center, Tehran University of Medical Sciences, Iran in the previous 10 years. The criteria for inclusion of patients as CNO/CRMO were mono-, oligo- or multifocal inflammatory bone lesions (osteomyelitis, osteitis, osteosclerosis) by imaging techniques; duration of complaints for > 6 weeks; and onset before 18 years of age.ResultsThirty-nine patients were enrolled. Diagnosis of five patients were found compatible with monogenic ABDs. There were four sites of bone involvement per patient. The most common sites were vertebrae, pelvis, and tibia. Eight patients (23%) had dermatologic manifestations, including three psoriasis cases and one palmar pustulosis. All patients received NSAIDs, and 85% received it as first-line. Treatment was escalated to methotrexate or prednisolone when response was suboptimal. Out of 17 patients primarily treated only with NSAIDs, 47% remitted. In general, 84% of our patients are in remission: 36% without medication and 48% with medication.ConclusionOur CRMO patients showed an acceptable remission response to the current treatment regimen. Results of bone scintigraphy in suspected CRMO patients should be interpreted cautiously as an adjunct to clinical investigations. Special attention should be paid to extraosseous manifestations in suspected CRMO patients to avoid overlooking monogenic ABDs.Clinical trial numberNot applicable.

ABSTRACTAutoinflammatory diseases (AIDs) are defined as abnormal activation of the innate immune system leading to spontaneous and uncontrolled inflammation. AIDs may affect bone tissue and lead to chronic recurrent multifocal osteomyelitis (CRMO). However, the etiology and treatment of CRMO remain elusive. In previous studies, we reported that loss of Morrbid prevents myeloid-lineage leukemogenesis. Here, we observed that Morrbid and Pstpip2 are co-expressed in mature myeloid cells and hypothesize a pathogenic role for Morrbid in osteomyelitis. We generated a Pstpip2−/− strain with a 5-bp deletion in Pstpip2, and the strain manifests CRMO-like phenotypes. Loss of Morrbid in Pstpip2−/− mice significantly inhibited the initiation and progression of CRMO symptoms and mitigated activation of myeloid cells and the excessive release of inflammatory cytokines. In addition, single-cell transcriptome analysis demonstrated reduction of osteoclasts and inflammatory cells caused by loss of Morrbid in the Pstpip2−/−Morrbid−/− compound mutants. Using murine models, this study profiles the pathological cell landscape of CRMO by single-cell analysis and suggests that reducing the lifespan of inflammatory myeloid cells by targeting Morrbid can be an effective therapy for chronic osteomyelitis.

Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterised by aseptic inflammation of bone tissue. The number of patients and the clinical picture of CNO/CRMO in Japan are unknown; therefore, we conducted the first nationwide epidemiological survey. In the primary survey, the number of patients diagnosed with CNO/CRMO between 2015 and 2019 in paediatrics, rheumatology, orthopaedic surgery and dermatology departments of various institutions was investigated. In the second survey, the clinical pictures of these patients were assessed. The primary survey reported 289 patients, and the estimated number of patients nationwide was 434 (95% confidence interval, 367-501). The second survey analysed 205 patients. The median number of radiological bone lesions was three and the bone affected most frequently was the tibia. Tumour necrosis factor inhibitors showed higher efficacy and lower relapse rates than non-steroidal anti-inflammatory drugs or bisphosphonates. Cases that responded to tocilizumab and canakinumab were also reported. Earlier diagnosis was associated with higher rates of symptom- or drug-free status at the last follow-up visit. This is the first nationwide study in Japan, and one of the largest multi-centre studies worldwide, to provide comprehensive epidemiological data about CNO/CRMO.

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disease with clinical and radiological symptoms that overlap with fibrous dysplasia (FD), particularly in children. This study aimed to compare the clinical and radiological features of craniofacial CRMO and FD in a pediatric population. Seven children with CRMO and 14 with FD were retrospectively identified in our tertiary centre between 2012 and 2022. Their clinical, radiological, and biological (when available) data were collected. Two experienced radiologists reviewed imaging modalities following a standardized form, including characteristics of the lesions, soft-tissue involvement, and signal abnormalities (MRI). Swelling and pain were common symptoms in the CRMO group (7/7 and 5/5, respectively), compared with 11/14 and 2/14 patients in the FD group. Imaging (CT scan) comparisons revealed a predominance of erosive lesions, cortical interruption, periosteal apposition, and soft-tissue involvement in CRMO compared with FD (4/5 vs 0/6, p1=0.01; 5/5 vs 1/6, p2=0.01; 5/5 vs 0/6, p3=0.002; and 4/5 vs 0/6, p4=0.02, respectively). Hyperosteosis was mainly associated with FD lesions (6/6 vs 2/5, p=0.06). Knowledge of the clinical and radiographic differences between CRMO and FD could help clinicians to differentiate between the two diseases.

Rare imaging features of adult chronic recurrent multifocal osteomyelitis on PET/CT.

Abstract Background/Aims Chronic Recurrent Multifocal Osteomyelitis (CRMO) or Chronic non-bacterial osteomyelitis (CNO) is a rare inflammatory bone disorder mainly affecting children and young adults. The time from onset of symptoms to diagnosis is often delayed due to variety of reasons. There is little evidence for treatment of this condition, which is often empiric, based on personal experience, expert opinion, case reports or small case series. In 2018, the Eurofever registry published the largest case series and complete remission of symptoms was largest in the group of patients treated with bisphosphonates (51%). Much of the available evidence about the use of bisphosphonates is with pamidronate. However, zoledronate has been increasingly used due to its efficacy in other bone disease, longer duration of action, and possibly fewer infusions. In this small case series, we aimed to review the response of patients with CRMO to zoledronate. Methods This was a retrospective study, collecting data from electronic medical records of 8 consecutive patients with CRMO treated with zoledronate by the Paediatric Rheumatology team at Nottingham Children’s Hospital since 2021. Results 8 patients treated with zoledronate were identified. Of these 3 (37.5%) were female and 5 (62.5%) were male. Additional demographic data was unavailable for 1 patient. In the remaining 7 patients the age of onset of symptoms ranged from 6 years to 14 years with a mean age of onset of 9 years. The length of symptoms before rheumatology review ranged from 2.5 months to 36 months with a mean of 13 months. The commonest sites involved were Femur (71%), followed by mandible (42%) and pelvis (29%). All 8 patients had received a trial of NSAIDS before receiving zoledronate. All patients received concurrent treatment with IV methylprednisolone along with zoledronate. The indications of zoledronate treatment were symptoms persisting despite NSAIDs and spinal lesions, even if asymptomatic. The protocol involves giving a single dose of zoledronate with subsequent doses given only if there is a clinical and / or radiological flare. No patients reported significant side effects. 7 (87.5%) patients had a response to zoledronate. 6 patients have received only 1 infusion of zoledronate. 1 patient received 3 zoledronate infusions in total with a second dose given 12 months after the first one and the third dose 16 months following the second. The other patient had two zoledronate infusions 12 months apart. Conclusion The data confirms previous evidence that bisphosphonates are a safe and effective treatment in children and adolescents with CRMO, with zoledronate specifically being effective without significant side-effects. As this is a retrospective study there were limitations to the data collected. Prospective studies looking at the treatment of CRMO are needed to help develop a standard approach to management of these patients. Disclosure M.C. Mackay: None. S. Deepak: None. K. Gargh: None. S. Rangaraj: None. K. Warrier: None.

Whole-body magnetic resonance imaging (WB-MRI) can effectively diagnose rheumatologic diseases with systemic and multifocal characteristics, such as spondyloarthritis, chronic recurrent multifocal osteomyelitis, and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, among others. Advances in rheumatic disease treatments have emphasized the importance of early diagnosis for effective management, function preservation, and improved quality of life. WB-MRI offers comprehensive imaging of the musculoskeletal system, detecting early and subtle disease changes that traditional methods might overlook. Initially used for spondyloarthritis, the technique has recently expanded to other rheumatic diseases and is becoming the gold standard for diagnosing and monitoring chronic nonbacterial osteomyelitis in pediatric patients. This review article presents the current status of WB-MRI in rheumatologic conditions.

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.

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.

426 Chronic recurrent multifocal osteomyelitis masking as acute rheumatic fever