ObjectiveBehçet’s disease (BD) may initially manifest solely with mucocutaneous involvement. This study aimed to identify demographic and clinical factors associated with subsequent intestinal involvement in patients presenting exclusively with mucocutaneous manifestations during early disease stages.MethodsData were obtained from the International AutoInflammatory Disease Alliance Network registry dedicated to BD; a Bayesian statistical approach was employed to address the limited sample size resulting from subgroup stratifications.ResultsIn total, 328 BD patients with exclusively mucocutaneous onset were enrolled; of these, 46 (14%) developed intestinal involvement over time. The risk of ocular involvement was higher among patients with intestinal manifestations (OR: 3.02, 95% CrI: 1.24–6.08; posterior probability: 99.3%). Minor aphthous ulcers without major aphthosis were protective towards intestinal involvement (OR: 0.47, 95% CrI: 0.22–0.98; posterior probability: 97.98%). Conversely, major aphthous ulcers increased the risk (OR: 3.25, 95% CrI: 1.50–7.02; posterior probability: 99.7%), along with the combination of oral major aphthosis with: i) genital aphthosis (OR = 2.77, 95%CrI: 1.14-6.58; posterior probability: 98.45%); ii) pseudofolliculitis (OR = 3.18, 95%CrI: 1.15-8.33; posterior probability: 98.72%); iii) genital aphthosis plus pseudofolliculitis (OR = 5.22, 95%CrI: 1.71-16.35; posterior probability of 99.77%). Pseudofolliculitis plus cutaneous manifestations other than erythema nodosum were protective against intestinal involvement (OR = 0.01, 95%CrI: 0.0-0.98; posterior probability: 97.55%).ConclusionMajor aphthosis was the strongest factor associated with intestinal involvement in BD patients initially presenting with mucocutaneous symptoms only. In such patients, intestinal involvement correlated with increased risk of ocular inflammation.

OBJECTIVES:The objective of this study was to develop and test a composite DAS for JDM solely based on parent-reported outcomes (PROs). METHODS:The parent JDM Activity Index (ParJDMAI) includes the following four PROs: (1) global assessment of disease activity; (2) assessment of fatigue; (3) assessment of muscle disease activity; (4) assessment of skin disease activity. Each item is weighted on a 0-10 scale, which yields a total score ranging from 0 to 40. Validation procedures were conducted on a multicentre sample of 254 patients with JDM according to the OMERACT filter for outcome measures in rheumatology. RESULTS:The ParJDMAI is short and simple, and is quick, taking <10 minutes to complete and score, which makes it practical for use in standard clinical care. In validation analyses, the tool demonstrated good construct validity, satisfactory internal consistency (Cronbach's alpha 0.86) and structure (with unambiguous identification of one factor with eigenvalue 2.9 on exploratory factor analysis), strong ability to discriminate between physician-estimated disease activity states (P < 0.001), and fair responsiveness to clinically important change over time (standardized response mean 0.8 among patients judged as improved by the parents). The ParJDMAI correlated strongly with physician-centred measures of disease activity. CONCLUSION:The ParJDMAI was found to be feasible and to possess good measurement properties. It also proved to potentially serve as a surrogate for physicians' evaluations. Completion of the ParJDMAI through digital technologies may provide a reliable and pragmatic approach for building a remote patient-monitoring program.

The transition of care from paediatric to adult healthcare services is a vulnerable period for patients with inborn errors of immunity (IEI), a heterogeneous group of primary immunodeficiency disorders characterized by chronic immune dysfunction and significant morbidity. With advances in diagnosis and treatment, an increasing number of patients with IEI are now reaching adulthood, making the management of this transition a growing clinical priority. Inadequate transition is associated with medical complications, treatment non-adherence, discontinuity of care, increased healthcare utilization, and poorer long-term outcomes. Despite growing awareness, condition-specific and standardized transition guidelines for IEI remain largely absent, leaving clinicians without a clear framework to guide this critical phase. In this context, the present review proposes a structured, multidisciplinary transition protocol designed specifically for paediatric patients with IEI to support therapeutic adherence, continuity of care, and patient well-being. This practice-informed narrative review integrates a non-systematic appraisal of the available literature, expert clinical consensus, and the practical experience of a dedicated Italian centre. Central to this model are the early identification of patients eligible for transition, beginning around age 14, and the gradual involvement of a multidisciplinary team, with shared responsibility between paediatric and adult specialists throughout an overlap period of at least three years. Clear documentation, including a standardized clinical dossier and final transition report, along with measurable process and outcome indicators such as infection rates, follow-up adherence, and patient-reported quality of life, ensures continuity of care and ongoing support. The framework also addresses immunoglobulin replacement therapy options, including intravenous, subcutaneous, and facilitated subcutaneous immunoglobulin, which each offer distinct advantages depending on patient needs and life stage. Patient and caregiver empowerment, timely management of comorbidities, and regular reassessment of individual needs are core components. Although resource-intensive, the proposed model is designed to be adaptable to different healthcare settings. Limitations, including reliance on multidisciplinary resources and the absence of prospective validation, are acknowledged, and future research to evaluate its impact on clinical outcomes is warranted. Through coordinated, standardized strategies, this work aims to bridge the gap between paediatric and adult healthcare, reducing care discontinuity and supporting successful long-term disease management in adulthood.

OBJECTIVES:The progression of Behçet's disease (BD) from a mucocutaneous-limited form to major organ involvement (MOI) represents a significant challenge. This study aims to identify patients without MOI at BD onset who are at increased risk of developing MOI in later stages. METHODS:Patients' data were drawn from the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. RESULTS:A total of 328 patients with exclusively mucocutaneous manifestations at BD onset were enrolled. Of these, 82 patients (25%) developed MOI over the entire follow-up period. Patients with minor oral aphthosis and no major oral aphthosis exhibited a reduced risk of developing MOI, with an odds ratio (OR) of 0.41 [95% confidence interval (95%CI): 0.22-0.79, P = 0.008]. Conversely, patients with both major and minor oral aphthosis had a significantly higher risk of developing MOI, with an OR of 12.76 (95%CI: 1.44-113, P = 0.02). Moreover, the development of MOI was associated with major oral aphthosis plus genital aphthosis (OR: 2.49, 95%CI: 1.1-5.6, P = 0.03), major oral aphthosis plus pseudofolliculitis (OR: 2.9, 95%CI: 1.15-7.4, P = 0.02) and major oral aphthosis plus both genital aphthosis and pseudofolliculitis (OR: 3.73, 95%CI: 1.22-11.4, P = 0.02). A positive family history for BD was associated with MOI (OR: 2.85, 95%CI: 1.08-7.58, P = 0.03). CONCLUSION:A positive family history and the presence of major oral aphthosis combined with minor oral aphthosis, genital aphthosis or pseudofolliculitis are associated with MOI development in patients with mucocutaneous BD at onset.

BACKGROUND AND OBJECTIVE:Clavicular pain and swelling in children can have multiple causes and often require a multidisciplinary approach. We aimed to describe the characteristics and final diagnoses of children with clavicular involvement and to review the literature on this topic. METHODS:We retrospectively reviewed patients younger than 18 years who were evaluated for clavicular symptoms at two pediatric rheumatology centers and one pediatric oncohematology center. These data were then descriptively compared with findings from 63 patients reported across 7 published articles. RESULTS:Twelve patients (9 females, median age 10 years [IQR 9.4-10.5]) were included. Final diagnoses were chronic nonbacterial osteomyelitis (CNO; 8), Langerhans cell histiocytosis (LCH; 2), reactive arthritis (1), and Tietze syndrome (1). Clavicular involvement was mostly unilateral and localized to the medial clavicle in CNO. The most frequent presenting symptom was local swelling (11/12), followed by pain (9/12). Diagnostic delay was a median of 4 months (IQR 1-10.5). Whole-body MRI revealed multifocal lesions in 6/8 CNO patients. Biopsy was often required for diagnosis primarily to exclude malignancy and to clarify atypical or unifocal presentations. The literature review confirmed CNO as the most frequent cause, followed by rare tumors. CONCLUSIONS:CNO predominates among pediatric non-traumatic clavicular lesions, but LCH and rare conditions are not uncommon, underscoring the need for careful differential diagnosis and targeted imaging.

BackgroundHematologic immune dysregulation (H-ID) – including autoimmune cytopenia (AIC), lymphoproliferation (LPD), and hemophagocytic lymphohistiocytosis (HLH) – is a potentially life-threatening manifestation of inborn errors of immunity (IEI). Despite the availability of targeted therapies, its management remains challenging, with no standardized treatment strategies established.ObjectiveTo evaluate the efficacy and safety of the available treatments for H-ID, with a specific focus on the treatment indications and outcome differences between targeted versus non-targeted therapies.MethodsThis multicentric retrospective study included 116 patients with IEI and H-ID across Italian tertiary care centers. Data included treatment indications, response rate, and incidence of adverse events (AEs).ResultsWe included patients with autoimmune lymphoproliferative immunodeficiencies (ALPID, 37.1%), humoral immunodeficiencies (31%), syndromic IEI (8.6%), and combined immunodeficiencies (8.6%). H-ID consisted of AIC (67.2%), LPD (71.6%), and HLH (9.5%). 85.3% of patients received treatment, including on-demand therapies (37.9%), long-term treatments (LTT, 84.8%), and hematopoietic stem-cell transplantation (HSCT; 9.1%). LTT included sirolimus (42.9%), mycophenolate mofetil (34.5%), rituximab (29.8%), and targeted therapies (17.9%). Sirolimus showed a higher complete response (CR) rate (61.1%), especially in ALPID patients and those with lymphoproliferation (72%). CR rate was significantly higher in patients receiving targeted therapies (80% vs 43.4%, p < 0.05). AEs were reported in 13.3% of cases, leading to drug withdrawal in 3.6%.ConclusionsThe indications for LTT and HSCT in H-ID are still heterogeneous. Response rates are variable and influenced by the underlying diagnosis. Targeted therapies are associated with an improved response, the suboptimal molecular diagnosis rate currently limits their use.

INTRODUCTION:Childhood-onset systemic lupus erythematosus (cSLE) accounts for 15-20% of all forms of SLE. It is associated with greater disease severity and requires more aggressive treatment than adult-onset SLE. Despite therapeutic advances, many patients do not achieve sustained remission, highlighting the need for more effective treatment strategies. AREAS COVERED:This review summarizes the literature published in the past two decades on the use of biologic medications for the treatment of cSLE. It is based on the narrative analysis of recent clinical trials, observational studies and patient series or individual clinical cases. We discuss the rationale, indications, effectiveness and safety of the biologic agents utilized thus far in patients with cSLE, with a primary focus on rituximab and belimumab. In addition, we address the future perspectives of the management of cSLE. EXPERT OPINION:The improved understanding of the mechanisms involved in immunopathogenesis of SLE has led to the development of increasing numbers of biologic agents that target specific cells or pathways. This advance has increased the therapeutic options available for the management of cSLE and holds great promise for transforming the landscape of cSLE care through the implementation of precision medicine and personalized therapeutic approaches, with the ultimate goal of reaching sustained, glucocorticoid-free disease remission.

Juvenile fibromyalgia (JFM) is a chronic pain condition affecting children and adolescents, often accompanied by emotional distress. Evidence suggests that autonomic dysregulation, as measured by reduced heart rate variability (HRV), may play a key role in symptom expression. This study aimed to explore clinical, emotional, and physiological differences between children with and without JFM. This observational cross-sectional study enrolled 30 participants aged 8 to 17, divided into two equal groups based on JFM diagnosis according to ACR 2010 criteria. Clinical evaluation included Widespread Pain Index (WPI), Symptom Severity Scale (SSS), Numerical Rating Scale (NRS), and the Multidimensional Anxiety Scale for Children – Second Edition (MASC-2). HRV coherence was measured using the emWave Pro system. Group comparisons were analyzed using non-parametric Wilcoxon tests. Correlations were assessed with Spearman’s rank-order test, and logistic regression was used to examine HRV as a predictor of JFM. Children with JFM showed significantly higher levels of pain and anxiety compared to controls (p < 0.001), and significantly lower HRV coherence (mean 0.91 vs. 1.27; p < 0.01). Inverse correlations were found between HRV and symptom severity (WPI, SSS) as well as anxiety levels. Reduced HRV coherence is associated with greater symptom burden and psychological distress in children with JFM. These preliminary findings suggest that HRV may represent a potential biomarker in pediatric fibromyalgia, but larger and more robust studies are required before drawing firm conclusions. HRV biofeedback may offer a supportive, non-pharmacological approach for improving autonomic regulation and managing chronic pain in youth. Not applicable. This observational study was not registered as it did not involve a healthcare intervention.

Pediatric hyperinflammatory diseases, including Still's disease, Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), and recurrent pericarditis (RP), represent a spectrum of conditions characterized by immune dysregulation and systemic inflammation. Each disorder exhibits distinct pathophysiological mechanisms and clinical features, yet their overlapping presentations often pose diagnostic challenges. Early and accurate differentiation is critical to mitigate complications such as macrophage activation syndrome (MAS), coronary artery aneurysms, and myocardial dysfunction. This narrative review explores the pathophysiology, diagnostic criteria, and management of these conditions, emphasizing the utility of advanced biomarkers, imaging modalities, and genetic testing. For Still's disease, the review highlights the transformative role of biologic therapies targeting IL-1 and IL-6 in reducing systemic inflammation and improving outcomes. In KD, timely administration of intravenous immunoglobulin (IVIG) and combination with high-dose steroids in high-risk patients is pivotal for preventing coronary complications. MIS-C, associated with SARS-CoV-2 infection, requires tailored immunomodulatory approaches, including corticosteroids and biologics, to address severe hyperinflammation and multiorgan involvement. RP management prioritizes NSAIDs, colchicine, and IL-1 inhibitors to reduce recurrence and corticosteroid dependence. The review advocates for a multidisciplinary approach, integrating standardized diagnostic algorithms and disease-specific expertise to optimize patient care. Future research directions include the identification of predictive biomarkers, exploration of novel therapeutic targets, and development of evidence-based treatment protocols to enhance long-term outcomes in pediatric inflammatory diseases.

Objectives:To detect factors capable of predicting the development of macular edema (ME) throughout the disease course in patients affected by non-infectious uveitis (NIU). Methods:Predictive factors leading to the development of ME were analyzed through regression analysis. The functional impact of ME on best corrected visual acuity (BCVA) was also examined. Results:A total of 1,160 NIU patients (1,857 eyes) were analyzed. ME was observed in 148 (12.76%), affecting 211 eyes. It was significantly more frequent in patients with non-anterior NIU (p < 0.0001, RR = 4.01), retinal vasculitis (p < 0.0001), and other structural complications (p = 0.0005). Gender, HLA-B*27 and/or HLA-B*51 positivity, and ethnicity did not show any significant impact on the prevalence of ME (p = 0.635, p = 0.372, p = 0.193, respectively). Four variables were associated with ME development during NIU course: the non-anterior anatomical pattern (p < 0.0001, OR = 4.01), the presence of retinal vasculitis (p = 0.028, OR = 1.68), complications other than ME (p = 0.044, OR = 1.51) and immunosuppressive treatment (p = 0.010, OR 1.69) while the diagnosis of Behçet disease-related uveitis was less likely to be associated with ME development (p = 0.24, OR 0.545). Mean ± SD BCVA was significantly lower in eyes with ME (0.82 ± 0.30) compared to eyes without ME (0.71 ± 0.33). Conclusion:ME can develop across all NIU types, but is more likely in cases involving the posterior segment and retinal vasculitis. Regular and focused monitoring is recommended for these high-risk patients. The study also highlights the limited predictive value of demographic and HLA-related factors, helping refine clinical risk stratification and predictive modeling in NIU.

Behçet’s disease (BD) frequently arises with exclusively mucocutaneous involvement, but some patients will develop major organ involvement, including ocular inflammation. This study aims to assess the patients’ demographic and clinical characteristics that may be associated with the development of ocular involvement in patients with BD with exclusively mucocutaneous involvement in the early stages. Patients’ data were collected in the International AutoInflammatory Disease Alliance (AIDA) Network registry dedicated to BD. A total of 328 patients with BD were enrolled, 36 (11

OBJECTIVES: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. METHODS: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. RESULTS: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. CONCLUSION: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.

This study aims to describe complications of pediatric-onset uveitis and their predictors among baseline and treatment-related factors. This registry-based observational study included patients with noninfectious uveitis with disease onset < 18 years. A total of 309 patients were enrolled (535 eyes). Uveitis was anterior in 290 eyes (54.2

The study objective was to compare the effectiveness of adalimumab (ADA) in monotherapy and in combination with methotrexate (MTX) for paediatric noninfectious uveitis (NIU). Registry-based observational study. Children receiving ADA for active uveitis were divided into the ADA monotherapy group (group 1) and the ADA plus MTX combination group (group 2). Eighty four children were enrolled (146 eyes): 22 in group 1 (26.2%) and 62 in group 2 (73.8%). ADA effectiveness was complete in 48 children (57.1%), partial in 23 (27.4%) and absent in 4 (5.3%), without any differences across the groups ( p  = 0.89). Fewer relapses per 100 PY occurred after ADA treatment both in group 1 (280.0 vs. 23.0, p  = 0.005) and in group 2 (297.9 vs. 86.0, p  < 0.001). The final BCVA was similar between groups 1 and 2 [median 1.0 (IQR 0.3) and 1.0 (IQR 0.3), respectively, p  = 0.55]. A statistically significant steroid-sparing effect was observed in the entire cohort and in group 2 at the 6-month ( p  = 0.01 and p  = 0.01), 12-month ( p  = 0.02 and p  = 0.02), and last follow-up ( p  = 0.045 and p  = 0.045). The estimated ADA retention rate was 97.1% at 12 months, 87.7% at 24 months, and 82.6% at 36 months, without a statistically significant difference among the groups ( p  = 0.77). ADA monotherapy could be equally effective as its combination with MTX in both preventing uveitis relapses and preserving visual acuity in paediatric NIU, with comparable retention rates over 36 months of treatment. The steroid-sparing effect of ADA monotherapy warrants further extensive evaluation to define its optimal placement in the therapeutic strategy for paediatric NIU.

The "biologic era" in the management of juvenile idiopathic arthritis (JIA) has begun in the year 2000, with the publication of the randomized controlled trial on etanercept. In the subsequent years, there has been continued progress, marked by the availability of new therapeutic agents and the shift towards early aggressive interventions. In addition, a more rational therapeutic approach has been fostered by the promulgation of therapeutic recommendations and guidelines. In parallel with the growing use of the novel biologic disease-modifying antirheumatic drugs (bDMARDs) in the real world of clinical practice, additional information has been gained about their effectiveness and safety. Furthermore, the role of the various bDMARDs in the management of the different JIA categories and of the main disease complications and comorbidities has been scrutinized. Innovative management strategies, such as the step-down and the treat-to-target, have been proposed to maximize the therapeutic benefits through the optimal combination of the newer and conventional medications. However, despite this progress several unmet needs remain, including the lack of well-established criteria for medication discontinuation after the attainment of sustained disease remission and of effective alternatives for patients who respond inadequately to the contemporary therapeutic modalities. The research agenda also calls for the search for reliable early predictors of therapeutic response that foster personalization of treatment and increase its precision. The aim of this Review is to summarize the evidence obtained in the past 5 years in the field of biologic therapy for JIA and to discuss the remaining gaps and the future perspectives of the use of these medications.

Musculoskeletal (MSK) symptoms are the most common extra-articular manifestations of pediatric-onset inflammatory bowel diseases (pIBD), and are associated with a more aggressive disease course. This study aims to characterize MSK manifestations in patients with pIBD, and to seek for predictors of persistently active arthritis one year after pIBD diagnosis. A multicenter, retrospective cohort study was conducted at 25 Italian pediatric rheumatology centers. Patients aged < 18 years with pIBD and MSK manifestations, followed for at least one year, were included. Data at onset of first MSK symptom, pIBD diagnosis, and one-year follow-up visit following pIBD diagnosis were collected. A total of 180 patients were included, 111 (61.7

OBJECTIVE OR PURPOSE:To investigate whether noninfectious uveitis (NIU) activity varies across reproductive life stages (RLS) according to sex. DESIGN:Observational, retrospective, cross-sectional registry-based study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS:The study recruited female patients with NIU (regardless of anatomical location or underlying etiology) as the main study group and male patients as controls to allow sex-based comparisons. They were enrolled in the AIDA Network Uveitis Registry between 2020 and 2025. METHODS, INTERVENTION, OR TESTING:RLS (prepuberal, early puberty, late puberty, reproductive, perimenopause, and podtmenopausal) were approximated using age intervals derived from epidemiological data. Study outcomes were flare frequency, anterior chamber cells (ACC), anterior chamber flare, vitreous haze, new posterior segment inflammatory signs, and immunosuppressive treatment (IST) exposure. RESULTS:Four hundred twenty-five female and 275 male patients were included. Median (IQR) relapse number in 12 months was 0.8 (1.3) [min 0.0-max 2.0] in prepuberty, 1.0 (2.0) [0.0-5.0] in early puberty, 0.0 (1.0) [0.0-5.0] in late puberty, 0.5 (1.0) [0.0-8.0] in reproductive age, 1.0 (1.0) [0.0-10.0] in perimenopause, and 0.5 (1.0) [0.0-7.5] in post-menopause (P = .014). There was a statistically significant interaction between RLS and sex (P = .044), with a perimenopausal peak retained only in women. In subjects with active anterior involvement, differences in the distribution of ACC grades among RLS were observed, with a peak in prepuberty and early puberty (P = .004). Proportions of subjects receiving IST were higher in prepuberty and puberty than in the remaining RLS (P = .012). CONCLUSIONS:RLS are clinically relevant modifiers of uveitis activity and should guide patient education, risk stratification, and therapy. Early puberty and perimenopause increase relapse risk; pediatric cases show more severe anterior inflammation and require more systemic IST.

BACKGROUND:The study objective was to compare the effectiveness of adalimumab (ADA) in monotherapy and in combination with methotrexate (MTX) for paediatric noninfectious uveitis (NIU). METHODS:Registry-based observational study. Children receiving ADA for active uveitis were divided into the ADA monotherapy group (group 1) and the ADA plus MTX combination group (group 2). RESULTS:Eighty four children were enrolled (146 eyes): 22 in group 1 (26.2%) and 62 in group 2 (73.8%). ADA effectiveness was complete in 48 children (57.1%), partial in 23 (27.4%) and absent in 4 (5.3%), without any differences across the groups (p = 0.89). Fewer relapses per 100 PY occurred after ADA treatment both in group 1 (280.0 vs. 23.0, p = 0.005) and in group 2 (297.9 vs. 86.0, p < 0.001). The final BCVA was similar between groups 1 and 2 [median 1.0 (IQR 0.3) and 1.0 (IQR 0.3), respectively, p = 0.55]. A statistically significant steroid-sparing effect was observed in the entire cohort and in group 2 at the 6-month (p = 0.01 and p = 0.01), 12-month (p = 0.02 and p = 0.02), and last follow-up (p = 0.045 and p = 0.045). The estimated ADA retention rate was 97.1% at 12 months, 87.7% at 24 months, and 82.6% at 36 months, without a statistically significant difference among the groups (p = 0.77). CONCLUSIONS:ADA monotherapy could be equally effective as its combination with MTX in both preventing uveitis relapses and preserving visual acuity in paediatric NIU, with comparable retention rates over 36 months of treatment. The steroid-sparing effect of ADA monotherapy warrants further extensive evaluation to define its optimal placement in the therapeutic strategy for paediatric NIU.

Background: SAPHO syndrome is a rare autoinflammatory disease characterized in children by chronic non-bacterial osteitis (CNO), associated to a heterogenous dermatological involvement, ranging from Palmo-plantar pustulosis (PPP), to psoriasis vulgaris (PV), acne, hidradenitis suppurativa (HS), and pyoderma gangrenosum (PG). A recent study [1] suggested the existence of two different disease clusters in pediatric SAPHO syndrome (pSAPHO) based on skin manifestations: an acne-HS-PG group (male prevalence and disease onset in puberal age with skin manifestations refractory to multiple treatments) and a PPP-PV group (female prevalence and disease onset in prepuberal age with osteoarticular manifestations). Objectives: to confirm the presence of different disease clusters of pSAPHO in an italian multicentric cohort of patients, and to evaluate the efficacy of the different treatments in pSAPHO syndrome, compared to CNO. Methods: SAPHO patients were enrolled in the Eurofever Registry and the data retrospectively analysed. Patients with pSAPHO were divided into an acne-HS-PG group and a PPP-PV group, and were compared to a CNO group without skin manifestations. Comparison of frequencies between groups was performed by the means of the Chi-square test or by the Fischer’s Exact test. Results: 43 pSAPHO patients with skin manifestations (32 acne-HS-PG and 11 PPP-PV) were enrolled and compared to 50 CNO. In the Acne-HS-PG group, 83.9% of the patients were males, with disease onset in puberal age with skin manifestations (median 13.7 years), and the appearance of osteoarticular symptoms in the following year in 81% of patients. In the PPP-PV group, 90.9% of patients were females, with disease onset in 100% of patients with osteoarticular manifestations in prepuberal years (median 10 years), and with the appearance of skin manifestations in the following year. In the CNO group there were no gender differences, with a median age at disease onset of 9.2 years. A statistically significant difference was found between the 3 groups in terms of sex (p< 0.0001), and between acne-HS-PG and PPP-PV and acne-Hs-PG and CNO for the age at disease onset (p< 0.0001) (Figure 1A). Moreover, a different osteoarticular involvement was evident in the 3 groups: all patients showed typical metaphyseal involvement, even if it was prevalent in the CNO group (86%, p=0.04), while an axial pattern (sterno-clavicular-spine-sacroiliacs) was more frequently present in the acne-HS-PG group (p<0.01), and a mandibular involvement in the PPP-PV group (p<0.01) (Figure 1b). The 3 groups presented also a different response to treatments: in the CNO group, NSAIDs, methotrexate and salazopyrin were more frequently used (p<0.05), and were efficacious in about 40% of patients, while 36% required bisphosphonates (BP), and 28% a biologic therapy. Similarly, in the PPP-PV group 30% of patients responded to NSAIDs alone, 30% to BP while 30% required the addition of a biological therapy. The skin responded well to the topical therapies or to DMARDs. In the acne-HS-PG group instead, there was a prevalent use of systemic steroids (50% of patients, p<0.05) and biological therapies (81% of patients, p<0.05). Among these, the combination Adalimumab/methotrexate was the more efficacious, with a remission achieved in 53% of patients. The skin resulted particularly difficult to treat in all the patients and was the cause of a therapy cycling. Conclusion: This study confirms the presence of 2 different disease clusters in pSAPHO based on the skin manifestations: an acne-HS-PG group characterized by a male predominance with puberal disease onset with skin manifestations particularly refractory to treatments, and a PPP-PV group characterized by female predominance with prepuberal disease onset with osteoarticular manifestations. These findings warrant a different therapeutical approach based on skin manifestations, and highlight the need of a new disease classification. REFERENCES: [1] Matucci-Cerinic C, et al. Semin Arthritis Rheum. 2023 Dec;63:152277. Acknowledgements: NIL. Disclosure of Interests: Caterina Matucci-Cerinic: None declared, Anna Attico: None declared, Clara Malattia: None declared, Alessandro Consolaro: None declared, Silvia Rosina: None declared, Luciana Breda: None declared, Saverio La Bella: None declared, Marco Cattalini: None declared, Francesca Ricci: None declared, Giovanni Conti: None declared, Adele Civino: None declared, Francesco Licciardi: None declared, Letizia Baldini: None declared, Antonella Insalaco: None declared, Francesco La Torre: None declared, Serena Pastore: None declared, Giovanni Filocamo: None declared, Gisella Beatrice Beretta: None declared, Gabriele Simonini: None declared, edoardo marrani: None declared, Angela Pistorio: None declared, Stefano Volpi SOBI, Roberta Caorsi: None declared, Nicolino Ruperto Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Abbvie, Aclaris, Amgen, AstraZeneca, Aurinia, BMS, Boehringer Ingelheim, Eli Lilly, Galapagos, Guidepoint, Janssen, Novartis, Pfizer, Sanofi., Gianmaria Viglizzo: None declared, Marco Gattorno Novartis, SOBI.Figure 1