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pMCTD is a rare disorder that includes features of systemic lupus erythematosus, polymyositis/dermatomyositis, juvenile idiopathic arthritis, and systemic sclerosis. Fifty years have passed since Sharp identified MCTD in 1972, and diagnosis of this disorder remains challenging. The aim of this review is to identify any clinical features at the diagnosis of pMCTD and manifestations that are not currently part of the available diagnostic criteria. A systematic literature review was performed in accordance with PRISMA guidelines using electronic bibliographic databases: MEDLINE via PubMed and EMBASE. Data obtained were extracted using a dedicated database containing clinical data that best categorize patient characteristics. Criteria for inclusion: studies including patients with a pMCTD diagnosis with onset before 18 years of age and reporting a description of initial clinical features. The search returned a total of 1372 results: 409 articles were excluded as duplicates and 790 based on title/abstract, 133 because of publication type (n = 4) or because the full text was not available (n = 65) or not in English (n = 64). One (n=1) eligible article resulted from manual screening of references cited in the selected publications and in the reviews. Finally, 41 articles were included: 23 case reports, 9 case series, 5 prospective, and 4 retrospective studies from 1973 to 2019, with a total number of 218 patients. They were predominantly female (81.56%, n=167), and the mean age at onset was 147 months (median 126 months, 10.5 years). When indicated, the most commonly used criteria for diagnosis were Kasukawa criteria (50%, 11 studies), then Alarcon-Segovia criteria (31%, 7 studies), then Sharp criteria (23%, 5 studies); no Khan criteria were used. Clinical features are listed in Figure 1. Joint involvement, Raynaud's phenomenon, myositis, and swollen fingers/hands are the most common clinical features at diagnosis according to the data reported in the literature, although with slightly lower percentages than in other reviews. Dermatologic signs are very heterogeneous, but were found to be a very present feature at disease onset, affecting 1/3 of patients. Fever, not covered by any of the diagnostic criteria, was noted in 1/4 of cases. Pulmonary and esophageal involvement are reported in a lower percentage at the onset of the disease, indicating a more developmental nature of these conditions. The data from this systematic review suggest greater clinical heterogeneity of the disease in the pediatric population, for which there are no validated diagnostic criteria. Typical features appear to be less common when case reports are included, suggesting a less characteristic initial presentation than an advanced stage; therefore, the absence of typical features at baseline should not preclude a diagnosis of pMCTD. Fever often occurs early in the disease and is not included in the diagnostic criteria. This systematic review may provide useful insights for future research to better assess the clinical features of pMCTD and the potential development of scores/algorithms for diagnosis in the pediatric population. [1] Sharp GC, Irvin WS, Tan EM, Gould RG, Holman HR (1972) Mixed connective tissue disease–an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 52(2):148–159 [2] Singsen BH, Swanson VL, Kornreich HK, et al. Mixed connective tissue disease in childhood: a clinical and serologic survey. J Pediatr 1977;90:893– 900. [3] Fraga A, Gudino J, Ramos-Niembro F, et al. Mixed connective tissue disease in childhood. Am J Dis Child 1978;132:263– 5. [4] Kahn MF, Appelboom T. In: Kahn MF, Peltier AP, Meyer O, editors. Les Maladies Systemiques. Paris: Flammarion; 1991. p. 545–56. [5] Sharp GC, Kasukawa R, Alarcon-Segovia D, Villarreal M. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue diseases and anti-nuclear antibodies. Amsterdam: Excerpta Medica; 1987. p. 23–48. NIL. None Declared. [Display omitted]

A recombinant vaccine is approved to prevent herpes zoster (HZ) in adults ≥50 years and immunocompromised individuals ≥19 years. However, in children, the live attenuated vaccine remains the only prevention strategy against varicella zoster virus (VZV), with only one trial evaluating the safety and immunogenicity of GlaxoSmithKline's HZ subunit candidate vaccine in immunocompromised children. To estimate VZV burden in our third level pediatric hospital and identify high-risk pediatric groups for its occurrence and complications to explore the need for an inactivated vaccine. We reviewed VZV/HZ hospital discharge codes and positive VZV molecular tests at Meyer Children's Hospital from January 2018 to May 2023. We categorized patients based on their vaccination status as unvaccinated, partially vaccinated (single dose), or fully vaccinated (complete two-dose regimen). 96 controls from the same Departments and period were also included to assess VZV vaccine effectiveness. Of 48 patients with VZV (52 % female; median age: 11.6 years [IQR: 7–14.2]), 10 had chickenpox and 38 HZ; 2/48 (4.2 %) received 2 doses of vaccination, 10/48 (20.8 %) were immunized with 1 dose and 36/48 (75 %) were unvaccinated. Immune-related comorbidities were present in 20/48 (42 %) patients, and among those with HZ requiring hospitalization, comorbidities strongly predicted admission (OR 4.71; 95 % CI, 1.23–20.39; p = 0.028). Full vaccination was more frequent in controls (43/96, 45 %) than in cases (2/48, 4.2 %; p < 0.001). In our cohort, many cases had comorbidities contraindicating the live attenuated vaccine. If proven safe and effective, the recombinant HZ vaccine could offer a preventive option for immunocompromised children ineligible for live viral vaccines. •The VZV live virus vaccine effectively prevents varicella and shingles.•Children with immunodeficiencies cannot receive live attenuated vaccines.•In our study, immunological comorbidities increase the risk of hospitalization.•A recombinant VZV vaccine is approved for immunocompromised patients aged 18 and older.•The inactivated VZV vaccine may offer preventive benefits for fragile children.

BackgroundJuvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. TNF inhibitors (TNFi) have dramatically changed the prognosis of this disease, but once achieved disease remission, it is not clear how and when stop therapy.ObjectivesOur purpose is to describe a multicentric cohort of JIA patients treated with the first course of Adalimumab and Etanercept in whom therapy was discontinued to persistent remission and identify predictors of relapse.MethodsIn a multicentric Italian retrospective study (Florence, Brescia, Trieste and Bari), patients with oligoarticular and polyarticular JIA were enrolled if they stopped therapy for persistent remission after the first course of Adalimumab and Etanercept. We collected demographic, clinical and laboratory data at onset and during biologic treatment.Results136 patients were enrolled (102 female, median age at onset 3 years (R1-15)), of whom 76 (55.9%) had oligoarticular JIA and 55 (40.4%) had uveitis. ANA positivity was found in 99(72.8%) (Table 1). TNFis were started at median age of 6 years (R1-16), with a median time intercourse between TNFi initiation and diagnosis of 12 months (0-127m). Seventy-nine (59.3%) were treated with ADA, and 57 (40.7%) with ETA. Remission was achieved after a median time of 4 months (R 1-32) and TNFi was discontinued after a median time of 30 months (R 6-90). TNFi were stopped in the 76.5% increasing the interval of administration, 18.4% reducing the dose, and 16.9% abrupt discontinuation. 106 patients (79.4%) relapsed after a median time of 6 months (R 0.5-96) for arthritis in 71 (66.9%), uveitis in 19 (17.9%), both in 18 (16.9%). Patients who relapsed were more frequently female (χ² 5.9 p<0.014), had history of uveitis (χ² 7.4 p<0.006), younger at onset (median 3 vs 7, p<0.001) and when TNFi was started (6 vs 9.5, p 0.002). Moreover, the time intercourse between diagnosis and TNFi initiation was longer (13 vs 8.5 months, p 0.02) and the weaned of therapy happened in shorter time (6 vs 9 m, p 0.005) (Table 1). Patients who not-relapse suspended TNFi more frequently lengthening intervals of administration (χ² 5.2 p0.015). Relapse free survival curve after withdrawal evaluated with Kaplan-Meier showed that patients with uveitis had a significantly earlier relapse (Log Rank χ² = 12.8 p <0.0001)ConclusionAlthough this is a retrospective study, we highlighted that early age at onset and at TNFi initiation, presence of uveitis and a long time to start biologics seem to be significantly more frequent in subjects who relapse, while stop therapy lengthening the interval of drug administration might be protective.Table 1.Characteristics of JIA patients after drug withdrawal (relapse Vs no-relapse)Entire cohort(136) n (%)Not relapse(28)Relapse(108)Test and p valueFemale n, %102 (75%)16 (57.1%)86 (79.1%)χ² 5.9 p 0.014Age at diagnosis, years, m (R)3 (1-15)7 (1-15)3 (1-11)p<0.001Uveitis history, n (%)55 (40.4%)550χ² 7.4 p<0.006Type of JIApOligo n (%)eOligo n (%)Poli n (%)55 (40.4%)21 (15.4%)60 (44.1%)12313431847nsANA positivity99 (72.8%)1683χ² 4.3 p 0.03Comorbdity n291019χ²4.35 p 0.037HLA B271467χ²3.9 p 0.048Type of BiologicsADA 79ETA 57ADA 13ETA 15ADA 66ETA 42nsCharacteristics at biologic starting and withdrawalAge at B initiation years, m, R6 (1-16)9.5 (1-15)6 (1-16)p0.002Concomitant therapy111 MTX (81.6%)20(71.4%)91(84.2%)χ² 6.58 p 0.03Time between diagnosis and B (months)12 (0-127)8.5 (0-117)13 (1-127)p0.021Time free from relapse out of therapy months6 (0.5-96)16 (4-96)5 (0.5-66)p<0.001Type of flareArthritisUveitisBoth71 (66.9%)19 (17.9%)18 (16.9%)-711918nsContinuation of concomitant therapy after stop B63339χ² 0.68 p 0.43N of months to stop B6 (0-22)9 (0-22)6 (0-22)p 0.005Modality to stop BLengthening intervalsReduction of doseAbrupt104 (76.5%)25 (18.4)16 (11.8%)26(92.8%)4178 (72.2%)2115χ² 5.2 p0.02Abbreviations: n number, m median, R range, pOligo persistent oligoarthritis, eOligo: extended oligoarthritis, Poli polyarticular, B biologic, ns: non significantREFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

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.Figure 1.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.

Background:Chronic nonbacterial osteomyelitis (CNO) is an autoinflammatory bone disease that mainly affects children and adolescents. Disease monitoring is challenging as reported pain is not reliable and imaging is not always obtained at all clinic visits. To date, patient reported outcomes used in CNO research have not yet been validated in this population. The Patient-reported Outcomes Measurement Information System (PROMIS) questionnaires, validated in other pediatric rheumatic diseases, are administered to patients enrolled in the prospective multisite CHronic nonbacterial Osteomyelitis International Registry (CHOIR)1 since 2018.Objectives:To assess the convergent and responsive validity of the PROMIS instruments in patients with CNO.Methods:Children or young adults with CNO were consented and enrolled into CHOIR. Self-reported PROMIS questionnaires of fatigue, pain interference (PI), pain behavior (PB), mobility, upper extremity (UE), physical activity (PA) and strength impact (SI) were administered to patients 8 years and older in English or Spanish at each clinical visit. Demographic, clinical, and imaging data were prospectively collected. The T score was calculated. External validation surveys were administered to assess patients’ perception of difficulty of use of limb/back/jaw, fatigue, sadness and worry on a 0-10 scale, disease status (inactive, mild, moderate, severe), and status change (unchanged, worsened, improved). Improvement of clinical disease activity score (CDAS) of 2.5 was defined as meaningful change. Descriptive statistics were used for demographic and clinical characteristics. Log-transformed linear mixed effect models with random participant intercepts were performed to assess PROMIS score changes after treatment. Wilcoxon signed-rank test with continuity correction was performed to determine the change of the PROMIS scores among the improved, worsened, and unchanged groups. Spearman rank correlation test was performed to determine the relationship between the PROMIS scores and reported disease status by patient/families.Results:More than 1,000 clinical visits from 184 patients were associated with self-reported PROMIS questionnaire entries in English. The median age at disease onset, diagnosis, and enrollment were 9.4 (IQR 7.5 – 11.3), 10.4 (IQR 8.4 -12.3), and 11.4 (IQR 9.5 – 13.8) years respectively. Seventy (38%) were males and 153 (83%) were White. All PROMIS scores correlated significantly (p<0.01) with patient reported variables and physician global assessment (PHGA). The correlation with function and PHGA was good (0.4-0.6) for Mobility, PB, and PI. All PROMIS scores, except physical activity, correlated significantly (p<0.05) with patient reported disease status. The correlation between patient-reported disease status and PHGA (0.75) was strong, moderate with Mobility (-0.53), PB (0.57), PI (0.5), and Fatigue (0.36), and weak with, SI (-0.23), UE (-0.23), and PA (-0.03). The changes of PROMIS scores over time for Mobility (p=0.015), PB (p<0.001), PA (p=0.019), and PI (p=0.011) compared to the self-reported status change (unchanged, improved, worsened) was significant. However, PROMIS score changes for Fatigue (p=0.055), SI (p=0.878), and UE (p=0.086) did not differ across various self-reported status change groups. After effective treatment when clinical disease activity score improved by at least 2.5 points (n=18), the change of PROMIS score from Mobility, PB, PI, UE was significant (p<0.05), whereas the change of PROMIS score from Fatigue, SI, and PA were not.Conclusion:PROMIS Questionnaires provide valuable information about disease status of children with CNO and correlate well with self-reported functional and other psychosocial domains. Mobility, PI, and PB show sensitivity to change after effective treatment or with disease status change. These instruments are useful for CNO clinical disease monitoring and research.REFERENCES:[1] Wu EY, Oliver M, Scheck J, et al. J Rheumatol. 2023 PMID: 37399459; PMCID: PMC10543471.Acknowledgements:The authors thank the CHOIR participants, research assistants and volunteers at all sites including Teresa Dickson, Corinne Lawler, Sumaya Aden, Thuan Bui, Kyra Shelton, Esha Mahal, Annie Xu, Kellen James, Shayla Nguyen, Zheng Xu, Ava Klein, Chessie Snider, Mabel Ho, Trang Pham, Anna Saack, Paige Trunnell, Emily Deng, Ana Park, Cailey Karshmer, Emma Leisinger, Mary Ellen Riordan, and Justine Griswold. We appreciate the help from Ingrid Goh, Mariana Correia Marques, and Min-Lee Chang for the testing of the registry database and the training material. In addition to the authors, the following CARRA CNO workgroup members participated in the February 2021 meeting: Ingrid Goh, Brian Nolan, Tzielan Lee, Annette Jansson, Aleksander Lenert, Lina Jaberi, David Cabral, Lauren Potts, Arielle Hay, Karine Toupin-April, Akaluck Thatayatikom, Ingram Chang, Piya Lahiry, Anja Schnabel, Mikhail Kostik, Nathan Rogers, Achille Marino, Dita Cebecauerova, Phillip Mease, Lindsey Bergstrom, Suzanne Li, Deborah McCurdy, Alex Theos, Matthew Hollander, Samira Nazzar, Farzana Nuruzzaman, Beverley Shea, and Chris Obrien. Statistical analysis was supported by CRMO Warriors Guild and Kaila’s Komfort generous donations.Disclosure of Interests:Yongdong Zhao Bristol-Myer Squibbs, Mary Eckert: None declared, Evelyn Yawei Wu I have worked as a paid consultant for 2 pharma companies – Enzyvant Therapeutics, Inc. and Pharming Healthcare, Inc., Melissa Oliver: None declared, Joshua Scheck: None declared, Sivia Lapidus: None declared, Ummusen Kaya Akca: None declared, Shima Yasin: None declared, Aleksander Lenert: None declared, Sara Stern: None declared, Antonella Insalaco: None declared, Manuela Pardeo: None declared, Gabriele Simonini: None declared, Edoardo Marrani: None declared, Xing Wang: None declared, Bin Huang: None declared, Leonard K Kovallick: None declared, Natalie Rosenwasser: None declared, Erin Balay: None declared, Gabriel Casselman: None declared, Adriel Liau: None declared, Ava Klein: None declared, Yurong Shao: None declared, Claire Yang: None declared, Molly Briggs: None declared, Ethan Mueller: None declared, Emily Deng: None declared, Paige Rhiannon Trunnell: None declared, Iris Hamilton: None declared, Elise Machrone: None declared, Doaa Mosad Mosa: None declared, Lori Tucker: None declared, Hermann Girschick: None declared, Ronald Laxer Akros Pharmaceutical, Eli Lilly Canada, Sanofi, Novartis, Sobi all less that 5000, Georgina Tiller: None declared, Jonathan Akikusa I have been on advisory boards in the last 12 months for Pfizer and Novartis with honoraria <$5000.I am an investigator in a drug trial for Abbvie., Christian Hedrich: None declared, Karen Onel: None declared, Fatma Dedeoglu: None declared, Marinka Twilt: None declared, Seza Ozen Novartis and SOBI and Bayer, Polly Ferguson I did provide consulting services last in 2020, Laura Schanberg: None declared, Bryce Reeve: None declared.

Background:Juvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. In adult patients diffuse subtype is associated with higher number of organ systems involvement. In a CARRA North American study, it was noted that 38% of jSSc patients had four or more organ systems involved. This topic has not yet been assessed in a large juvenile scleroderma inception cohort (jSSc) cohort.Objectives:To assess the number of organ systems involved in the diffuse and limited jSSc patients at the time of inclusion in the cohort.Methods:The jSSc is a prospective cohort including patients, who fulfill the adult SSc criteria[1], with first non-Raynaud symptom before the age of 16 years and under 18 years of age at the time of inclusion. We reviewed the number of organ systems involved at the time of inclusion into the cohort. The categorization of the organ system involvement was skin, vascular, muscular, articular, pulmonary, cardiac, gastrointestinal, renal and nervous system. We compared the number of involved systems between diffuse and limited jSSc subtype.Results:Until 1st of December 2023, 253 patients were enrolled and 177 of them had diffuse subtype. The median age at the onset of Raynaud´s was 10.4 years. The median age of the first non-Raynaud organ involvement was 10.9 years. The median disease duration was 2.5 years. The distribution of the cumulative organ involvement in the whole group and in the diffuse and limited subtype can be seen in Table 1. Similar to the CARRA study, a large number of jSSc patient had 4 or more organ systems involved, almost half of the cohort (46%). There was no significant difference between the cumulative number of organ systems involved between the SSc subtypes in the Inception cohort.Comparison of diffuse/limited jSSc at time of inclusion in the cohortWhole GroupN=253Diffuse SubtypeN=177Limited SubtypeN=76P valueNumber of organs involved0.22915% (13/253)3% (5/177)11% (8/76)221% (52/253)20% (35/177)22% (17/76)328% (72/253)29% (51/177)28% (21/76)423% (59/253)24% (43/177)21% (16/76)516% (40/253)18% (31/177)12% (9/76)66% (15/253)6% (11/177)5% (4/76)71% (2/253)1% (1/177)1% (1/76)80% (0/253)0% (0/177)0% (0/76)90% (0/253)0% (0/177)0% (0/76)Conclusion:In this largest jSSc cohort in the world, approximately half the enrolled children have 4 or more organ systems involved, which highlights the overall severity of the disease. There was no significant difference in jSSc children skin subtypes, lcSSc or dcSSc regarding, the cumulative number of organ systems involved, although as shown in our publications[2] the diffuse subtype presented more severe disease.This project was supported by an unrestricted grant from „Joachim Herz Stiftung“REFERENCES:[1] van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American college of rheumatology/European league against rheumatism collaborative initiative. Ann Rheum Dis. 2013 Nov;72(11):1747-55.[2] Foeldvari I, Klotsche J, Kasapcopur O, et al. Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort. Arthritis Care Res (Hoboken). 2022 Oct;74(10):1575-1584.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Juvenile systemic scleroderma (jSSc) is an orphan disease with a prevalence in 3 in 1 000 000 children. Positive nailfold capillaroscopy(NF+) finding correlate with more severe disease in adult systemic scleroderma[1]. There is currently no data, if this correlation does exist in jSSc.Objectives:To assess the difference in patients with jSSc with normal (NF-) and pathologic NF(NF+) findings at the time of inclusion in the cohort.Methods:Baseline data was extracted from patients enrolled in the juvenile scleroderma inception cohort that had nailfold capillaroscopy performed at inclusion [2] until 1st of December 2023. NF was performed by dermatoscope and/or high-resolution video nailfold capillaroscopy. We compared patients with NF+ and NF- findings from the baseline visit using chi-square test.Results:237 patients were included in the analysis, 185 (78%) of them were female. 126 (70%) had diffuse subtype. 183/237 patients (77%) were in the NF+ group. 71% in the NF+ group were Caucasian compared to 85% in the NF- group (p=0.051). Median disease duration was 2.3 years in the NF+ and 3.2 years in the NF- patients. Median age at onset of the first non-Raynaud´s was around 11 years in both groups. More patients in the NF+ group were ANA positive (95% compared to 79%, p <0.001). There was no difference in the anti-Scl70 or anti-centromere distribution.NF+ patients had significantly more frequent Raynaud phenomenon (96% compared to 78%, p<0.001); history of digital ulcerations (59% compared to 27%, p<0.001); abnormal high resolution CT findings of the lung (49% compared to 30%, p=0.034); overall gastrointestinal involvement (49% compared to 20%, p<0.001); oesophageal involvement (47% compared to 19%, p<0.001); musculoskeletal involvement (71% compared to 41%, p=0.003); presence of joints with decreased range (63% versus 45%, p=0.022) and presence of muscle weakness (25% compared to 3%, p=0.002). No significant differences were demonstrated in involvement of other organ systems such as skin, cardiac or renal. (see Table 1)Conclusion:In a jSSc cohort there were significantly more patients affected within various organ systems in those with nailfold capillary changes at enrollment compared to those without. Future studies should assess whether these differences persist over time.This project was supported by an unrestricted grant from “Joachim Herz Stiftung”REFERENCES:[1] Vanhaecke A, Cutolo M, Distler O, et al. Nailfold capillaroscopy in SSc: innocent bystander or promising biomarker for novel severe organ involvement/progression? Rheumatology (Oxford). 2022 Nov 2;61(11):4384-4396.[2] Foeldvari I, Klotsche J, Kasapcopur O, et al. Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort. Arthritis Care Res (Hoboken). 2022 Oct;74(10):1575-1584.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:In adult systemic sclerosis they are significant differences in clinical presentation of diffuse and limited subtype. In juvenile systemic sclerosis (jSSc) are the differences less prominent as we reviewed last time in a publication for the first 150 patients [1] of the juvenile scleroderma inception cohort (jSScC). The differences can change as the included number of patients is growing in the cohort.Objectives:To review the differences of clinical characteristics of patients and patient (PRO) and physician (PhRO) reported outcomes with limited jSSc (ljSSc) and diffuse (djSSc) subtype in the jSScC.Methods:We extracted date from the jSScC including patients who were enrolled till 1st f December 2023 into the cohort [1]. We compared the clinical characteristics, PRO and PhRO of the two subtypes and calculated statistical significance using chi-square test.Results:253 patients were included in the study. 70% (n=177) of the patients had diffuse subtype. Around 70% of the patients were Caucasian in both groups. The median age of onset of Raynaud’s were 10.1 in the djSSc and 11.8 years in the ljSSc. The median age at the time of the first non-Raynaud was 10.5 years in the djSSc and 12.0 years in the ljSSc. Looking at antibody profile the anti-centromere antibodies were significantly more frequent in ljSSc (11% versus 3%, p=0.025). djSSc patients had significantly higher (Table 1). Modified Rodnan skin score (16 versus 4, p=0.002), more frequently Gottron papules (32% versus 15%, p=0.004), with sclerodactyly (85% versus 54%, p <0.001), with telangiectasia (42% versus 21%, p=0.003), with history of ulceration (61% versus 30%, p<0.001)), with decreased Body mass Index <2 standard deviation(19% versus 6%, p=0.008), and presence of joints with decreased range of motion (65% versus 46%, p=0.004). None of the patients had renal crisis. There was no significant difference in cardiopulmonary and gastrointestinal involvement. Looking at PRO and PhRO in all categories djSSc patients had significantly more severe disease (Table 2).Conclusion:This results present a different organ involvement pattern form adults. Despite more severe disease according to patient and physician reported outcomes, we found no significant differences in the cardiopulmonary and gastrointestinal involvement between the subtypes. The antibody profile anti-Scl70 and anti-PMscl was not different between subtypes either.This project was supported by an unrestricted grant from „Joachim Herz Stiftung“REFERENCES:[1] Foeldvari I, Klotsche J, Kasapcopur O, et al. Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort. Arthritis Care Res (Hoboken). 2022 Oct;74(10):1575-1584.Acknowledgements:NIL.Disclosure of Interests:None declared.

BackgroundJuvenile systemic sclerosis (jSSc) is an orphan disease with a prevalence of 3 in 1 000 000 children. In adult patients decreased body mass index (BMI) correlates with higher mortality. We hypothesized that jSSc patients with lower BMI at presentation have more severe organ involvement.ObjectivesTo compare the organ involvement pattern at inclusion into the cohort of jSSc patients with BMI ≤ -2 z score with the patients with higher BMI.MethodsWe reviewed the clinical characteristics of patients who were recruited to the juvenile jSScC till 1st of December 2022. We compared patients with BMI ≤ -2 z score with patients (lwgroup) with higher BMI (nlwgroup). jSScC is a prospective cohort of jSSc patients, who developed the first non-Raynaud´s symptom before the age of 16 years and are under the age of 18 years at the time of inclusion.ResultsAt the time of the evaluation, we had 232 patients in the cohort and 217 of them had BMI data to include in the evaluation. Thirty-three patients were in the lwgroup (15%) and 88% (n=29/33) of them diffuse subtype and in the nlwgroup 64% (113/177). The median age at onset of Raynaud phenomenon in the whole group was 10.6 years and the median age at the first non-Raynaud symptom in the whole group was 11.0 years. Median disease duration in the whole group was 2.4 years at the time of inclusion. Approximately 95% of the patients were treated with a DMARD. There were no statistically significant differences between the lwgroup compared to nlwgroup regarding antibody pattern, inflammatory marker or organ involvement pattern, except higher number of patients with Gottron papules (41% lwgroup vs 25% nlwgroup; p=0.01) and sclerodactylia (84% lwgroup vs 73 % nlwgroup; p=0.049). Regarding the patient related outcomes at inclusion in the cohort, the global disease activity by VAS 0-100 was 40 in both groups (p=0.032), but the patient global disease damage by VAS 0-100 was 50 in the lwgroup which was significantly higher compared to 30 nlwgroup (p=0.014).Table 1.Comparison of patients with different BMI z-scores at time of inclusion in the cohortZ-Score ≤ -2N=33Z-Score > -2 to < 2N=177P valueGottron Papules41%(13/32)25%(44/175)0.001Puffy Fingers13%(4/30)38%(61/159)0.049Sclerodactylie84%(27/32)73%(121/166)0.049Patient globaldisease damage50 (30 – 75)n=2730 (10 – 55)n=1330.014ConclusionIn our jSSc cohort, currently the largest of the world, we could not find any differences regarding major internal organ involvement in patients with lower BMI at time of inclusion in the cohort. Nevertheless, there is a significant difference in patient related outcomes regarding global organ damage between the two groups. The long-term prognosis of these patients should be addressed in future studies.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Juvenile systemic sclerosis (jSSc) is a rare disease in childhood. To date, no composite response index exists to assess treatment effect in jSSc patients. ACR CRISS score (probability of improvement ranging from 0 to 1 based on mRSS, FVC%, PtGA, MDGA and HAQ-DI) and revised ACR CRISS (rCRISS, proportion of patients who improve in ≥ 3/5 ACR CRISS core items by a certain percentage, e.g. 30%, except 5% for FVC) were developed by experts in the field as outcome measures in adult patients with SSc. In addition, the Ranked Composite Important Difference (RCID) score was recently introduced as anchor to the ACR CRISS. We aimed to study the applicability and performance of the ACR CRISS, rCRISS and RCID in a prospectively followed cohort of patients with diffuse cutaneous jSSc. Data from the international jSSc inceptions cohort were used for this analysis. The ACR CRISS, rCRISS and RCID were calculated between baseline and 12-months follow-up according to the scoring algorithms. Missing values in the core items were estimated by multiple imputation by chained equations. Here we aimed to determine the value of the response measures to detect clinically change defined by the anchor questions about change (much better or little better versus almost the same, little worse or much worse) in patients overall health due to scleroderma since the last visit provided by the treating physicians and parents or patients (aged > 12 years). We included 95 jSSc patients with diffuse cutaneous subtype with available baseline and 12-months visit. Seventy-nine percent were female, the mean age at enrollment was 13.0 (3.8) and the mean disease duration was 3.1 (2.8) years. Among 95 patients, 57% were treated with steroids, 47% with methotrexate, 27% with MMF and 3% with a biological at baseline. ACR CRISS showed a ceiling effect (>.998) in 51% and a floor effect (<0.005) in 26% of patients. Patients who reported at least moderate improvement had a median ACR CRISS of 0.99 and in mean 2.6 (1.3) core items that improved by ≥20% from baseline to 12-months follow-up. The rCRISS 20/30/50 responses were 59%/49%/33% in patients who reported improvement (table 1) and 25%/25%/8% in patients with worsening. The RCID was approximately normal distributed (mean 20.7, SD 43.4). Mean (SD) RCID for patients who reported worsening was -10.5 (38.6) vs RCID of 20.7 (45.2) for patients who reported improvement. RCID scores for physician reported anchors of worsening or improvement were 6.5 (44.2) and 18 (45.4), respectively. The concordance between a positive RCID score and rCRISS 20/30 was moderate (rCRISS 20 and RCID, 43%, kappa=0.43; rCRISS 30 and RCID, 38%, kappa=0.36). Our data confirmed the presence of a ceiling and floor effect of ACR CRISS as shown in studies of adult SSc patients. The CRISS, rCRISS and RCID response distinguished between patients who rated their disease course since last visit as worsened or improved. Future studies should focus on the determination of specific pediatric weights for the CRISS and RCID components rather than extrapolation from adult SSc. In general, the RCID offers a meaningful tool in order to determine response to therapy in future clinical trials in jSSc patients. NIL. NIL. None Declared. Table 1ACR CRISS, rCRISS and RCID score by patients and physicians ratings about scleroderma disease courseWorsening/ no improvement reported by patients(n=12)Improvement reported by patients(n=49)P valueWorsening/ no improvement reported by physicians(n=14)Improvement reported by physicians(n=50)P valueMedian ACR CRISS score (IQR)0.0 (0 to 0.75)0.99 (0 to 1.0)0.0070.35 (0 to 0.99)0.99 (0 to 1.0)0.037rCRISS response 20%3(25%)29 (59%)0.0345 (36%)29 (58%)0.140rCRISS response 30%3 (25%)24 (49%)0.1342 (14%)27 (54%)0.008rCRISS response 50%1 (8%)16 (33%)0.0920 (0%)18 (36%)0.008Mean RCID score (SD)-10.5 (38.6)20.7 (45.2)0.0316.5 (44.2)18 (45.4)0.411CRISS = Composite Response Index in Systemic Sclerosis; RCID=Ranked Compsoite Important Difference; rCRISS = revised Composite Response Index in Systemic Sclerosis; SD = standard deviation