Objective To describe and analyze the clinical and laboratory findings in a group of children diagnosed with scleroderma at Beijing Children's Hospital in the last 10 years.Methods The clinical charts of children with scleroderma in the Rheumatology Department at Beijing Children's Hospital,between January 2002 and October 2013 were reviewed.All of them fulfilled the classification criteria for juvenile sclerodema,both systemic scleroderma (SSc) and localized scleroderma (LS) types.T test was used for comparison between the two groups.Results Forty-six patients were enrolled and were diagnosed as scleroderma.Seven patients(15％) suffered from SSc and 39 patients(85％) were LS.Mean age-at-onset of LS was (5±4) years old.The male to female ratio was 1.2:1.Mean age-at-onset of SSc was (9±4) years old.All patients were female.The lesions found in LS were linear scleroderma (54％),mixed morphea (36％),generalized morphea (8％),and panclerotic morphea (3％).Twenty-six patients had internal organs involved.Three patients with nerve system involvement was found in en coup de sabre (ECDS).Systemic involvement included lung and gastrointestinal tract primarily.The heart,nerve system,kidney,eye involvement was also found.One girl had SSc combined with renal crisis.Antinuclear antibodies were positive in 77％ of LS patients and 100％ of SSc patients.Rheumatic factor was positive in 6 patients (15％),5 patients had joint involvement.Tests for anti-Scl-70 antibodies were positive in 5 (71％) patients with SSc.The most common drugs used were methotrexate and prednisone.Conclusion In this study,LS is common in children.SSc is more severe than LS.Multi-center and large sample study is needed to know the characteristics of juvenile scleroderma in China.

Objective: To analyze the clinical data of children with rheumatic diseases complicated with osteonecrosis and summarize the clinical characteristics, so as to guide clinical work. Methods: The clinical data of 59 children with rheumatic diseases complicated with osteonecrosis from January 2010 to July 2018 were collected and analyzed retrospectively. Results: Among 59 children with rheumatic diseases complicated with bone infarction, 25 cases were systemic lupus erythematosus (SLE), 4 cases were mixed connective tissue disease, 6 cases were juvenile dermatomyositis, 1 case was Takayasu arteritis, 1 case was leukocy to clystic vasculitis, 13 cases were systemic onset juvenile idiopathic arthritis (SJIA), 1 case was polyarthritis, and 8 cases were juvenile ankylosing spondylitis. The median time from the onset of rheumatic diseases to osteonecrosis onset was 18 (7.00, 38.75) months. A total of 115 joints were involved in 59 children, the most common of which were bilateral hips and knees. Twenty-five were single joint involvement and 34 were multiple joints involvement. There were 37 cases (63%) with vasculitis, 9 cases (15%) with oralulcer, 5 cases (8%) with Raynaud's phenomenon, 31 cases (53%) with Cushing's face, 18 cases (31%) with kidney involvement, 25 cases (42%) with hypertension, and 12 cases (24%) with spinal compression frac- tures. According to statistics, 10 children with osteonecrosis occurred without glucocorticoid intake. The longest duration of glucocorticoid therapy was 13 years, and the average duration was about (27±35) months whensymptomatic osteonecrosis occurred. The median cumulative dose of prednisone was 381.9(209.77, 561.19) mg/kg. Conclusion SLE, SJIA and juvenile ankylosing spondylitis are the three most common rheumatic diseases in children with osteonecrosis. The locations of osteonecrosis are mostly the bilateral hips and knees. It is necessary to strengthen joint examination, physical examination and imaging screening for children with rheumatic diseases after 18 months of onset, so early detection, early treatment are the strategy to improve the prognosis of the diseases.

Objective:To analyze the outcome of 15 cases with refractory systemic lupus erythematosus (SLE) treated with Belimumab, and evaluate the safety and efficacy of the therapy.Methods:A retrospective and real-world clinical research method was adopted.Fifteen children with confirmed refractory SLE and complete follow-up data were selected from the Department of Rheumatology, Beijing Children′s Hospital from April 1, 2020 to March 31, 2022.By comparing the changes of clinical symptoms, auxiliary examination results, SLE disease activity index (SLEDAI-2000) and Physician′s Global Assessment (PGA) scores as well as adverse events in different treatment periods (before treatment, 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatment), the safety and effectiveness of Belimumab treatment were all recorded.The counting data was expressed in percentage, the measurement data meeting the normal distribution was expressed in Mean±SD, and the two samples of measurement data were compared by t-test, P<0.05 means significant differences. Results:The ratio of male to female was 3∶2, and the onset age was (7.93±4.99) years; The basic treatment time was 4 months to 5 years and 1 month.There were 8 cases with lupus nephritis (LN), 2 cases suffering from hypocomplementemia for more than 1 year, 2 cases with central nervous system involvements, 2 cases complicated with antiphospholipid syndrome and 1 case with early-onset SLE.Of 8 LN cases, 1 case was complicated with neuropsychiatric lupus (NPLE) and distal femoral head infarction of both knees, and 3 cases were complicated with lumbar compression fractures and hip infarction.All patients were treated with regular traditional therapy to induce remission.During the maintenance period, the disease activity maintained at light to moderate levels, and it was difficult to reduce glucocorticoid.At baseline, SLEDAI-2000 score was 4-13, and PGA score was 1-2.50.Basic treatment includes glucocorticoids combined with immunosuppressants (Cyclosporine, Mycophenolate Mofetil, Leflunomide tablets) and antimalarial drugs, and Cyclophosphamide and/or Tripterygium Wilfordii were used at the same time according to the damage of target organs.The drug safety after intravenous injection of Belizumab showed that one patient in this group had respiratory tract infection symptoms 4 weeks after treatment; Another patient had a slight increase of alanine aminotransferase 8 weeks after treatment, and recovered to normal symptomatic treatment.No drug-related adverse reactions were found in the other 13 patients.After 4 weeks of treatment, the score of SLEDAI-2000 and PGA compared with the baseline level, and the difference was statistically significant (SLEDAI-2000 P=0.002; PGA P=0.006). There was no clinical recurrence.One patient with familial chilblain like lupus erythematosus showed significant improvement in rash 2 weeks after treatment, and low fever accompanied by increased rash 8 weeks after treatment; After 16 weeks of treatment, the body temperature was normal and the rash basically subsided. Conclusions:Belimumab is clinically effective in the treatment of refractory childhood SLE, with no serious adverse events reported.However, its long-term efficacy and safety need to be further studied by multi-center and long-term research with a large sample size.

Objective:To compare the disease outcome, quality of life score [evaluated by child health assessment questionnaire - disability index(CHAQ-DI)] and medical expenses of children with systemic juvenile idiopathic (sJIA) combined with macrophage activation syndrome (MAS) diagnosed by two different criteria.And to analyze the impacts of early MAS diagnosis criteria on the prognosis of sJIA combined with MAS in children.Methods:From January 2016 to December 2020, children with high disease activity of sJIA who were diagnosed and initially treated in the Department of Rheumatology of Beijing Children′s Hospital were enrolled in this study.Clinical characteristics on admission were recorded as baselines.Patients were divided into 2 groups according to different diagnostic criteria.Children diagnosed as MAS based on the 2016 The European League Against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation MAS diagnostic criteria were included in MAS control group(38 cases), and those diagnosed as early MAS based on the sJIA combined MAS early warning scale but did not meet the 2016 diagnostic criteria were included in MAS early warning group(38 cases). Basic information, clinical manifestations and laboratory test results were collected.According to the clinical manifestations and laboratory results in different periods of follow-up at 4 weeks, 8 weeks, 12 weeks, 6 months and 12 months after treatments, the di-sease activity, CHAQ-DI and medical expenses were compared between the two groups.Results:There were no signi-ficant differences in the disease activity, duration of sJIA and medical expenses between the two groups (all P>0.05). In terms of laboratory results, serum ferritin in MAS early warning group were significantly lower than that of MAS control group at 4 weeks after treatment[(333.97±186.66) μg/L vs.(389.66±221.76) μg/L]( t=-83.47, P<0.05). In terms of disease activity, after 12 months of treatment, the evaluation of American College of Rheumatology pediatric indexes 70 in MAS early warning group was better than that in MAS control group [34.2%(13/38 cases) vs.7.9% (3/38 cases)]( χ2=6.067, P<0.05). In terms of CHAQ-DI, at 4 weeks, 8 weeks, 12 weeks and 6 months of treatment, CHAQ-DI in MAS early warning group were better than those in MAS control group, and the difference were statistically significant ( t=-0.34, -0.27, -0.23, -0.09; all P<0.05). In terms of cumulative medical expenditure at 12 months of treatment, the MAS early warning group was lower than the MAS control group [(114.3±80.7) thousand yuan vs.(157.9±111.7) thousand yuan]( t=-3.97, P<0.05). Conclusions:Quickly judge the condition through the quantitative integral of clinical examination and test indexes, screening and treatment of MAS in early stage are helpful to improve the prognosis and reduce the medical consumption.

Objective:To explore the clinical characteristic and prognosis of juvenile dermatomyositis (JDM) by retrospectively study of the clinical manifestations, laboratory examinations, treatment and follow-up results. The aim of this study was to improve the diagnosis and treatment of JDM and reduce the complications and mortality.Methods:Medical charts of 612 JDM cases hospitalized to Beijing children's hospital from July 2002 to July 2018. We retrospectively analyze the onset, clinical manifestations, laboratory examinations, treatment and the follow-up, and then summarize the clinical characteristics and assess the therapeutic effect and prognosis.Results:There were 278 male and 334 female. The maleto female ratio was 1∶1.2. Themedian age at symptoms onset was 5.4(2.9-8.4) years old (range 6 months to 14 years). Rash was the most common initial presentation. The main clinical manifestations were rash (100%, 612 cases) and muscles weakness (96.1%, 588 cases). The most commonly involved organs by JDM were lung (57.5%, 352 cases), digestive tract (38.5%, 236 cases) and heart (32.5%, 199 cases). Muscle enzymes elevated in 95.5% (584 cases) of the patients and 89.5%(534 cases) of the patients had typical changes on electromyography. Muscle biopsy was performed in 134 patients and pathologicresults were compatible with JDM. For the treatment, all of the patients were treated by steroids plus therapy combined with immunosuppressive agents. Mostof the patients got good effect and outcome. Twenty-four patients died, and acute respiratory failurewas the most common cause of death. 17.9%(105 cases) of patients had complications. The complications included calcinosis in 70 patients and amyotrophy in 35 patients.Conclusion:JDM is a rare disease of children, andis characterized by muscle weaknessand rash. Severe organ involvement may cause death. Treatments include corticosteroids and immunosuppressive agents, andthe outcome is generally good.

Objective:To evaluate the systemic involvement, outcome and other disease characteristics of children with systemic lupus erythematosus (cSLE), and to explore the prognostic factors.Methods:cSLE treated in Beijing Children′s Hospital, Capital Medical University from January 1, 2016 to December 31, 2017 were enrolled in this study.Medical records including clinical manifestations and evaluation of affected systems, autoantibodies, treatment adjustment, and follow-up were collected and analyzed retrospectively.SPSS 21.0 was used for statistical analysis and mapping.The prognostic factors were studied by the Cox proportional risk regression model.Results:A total of 210 children were included, including 37 males and 173 females, with a male to female ratio of 1.0∶4.7.The average age of onset was (121.39±30.44) months.There were 167 (79.5%) patients with skin and mucous membrane damage, 137(65.2%) patients with blood system damage, 129(61.4%) patients with digestive system damage, 123(58.6%) patients with kidney damage, 119(56.7%) patients with skeletal and musculoskeletal system damage, 71(33.8%) patients with nervous system damage, 68(32.4%) patients with heart damage, and 60(28.6%) patients with respiratory system damage.The 90.95%(191/210) of the children enrolled presented moderate or high disease activity at the first visit.The effective rate was 76.92% (150/195) after 1-month follow-up and 96.95% (159/164) after 1-year follow-up.A high level of compliment C 3 was a protective factor for disease remission.The glucocorticoid level was declined to 5 mg or less in 42 children, and the median time was 40.5 (36.0, 42.0) months.Young onset age and no renal damage were protective factors for glucocorticoid reduction. Conclusions:cSLE tends to occur in female children with multiple involved systems and severe conditions.After reasonable treatment and follow-up, the disease can be alleviated or improved in one year.A high level of complement C 3 at the beginning of disease is conducive to rapid remission of the disease, and the young age of onset and no renal damage is conducive to rapid glucocorticoid reduction.

Objective:To investigate the clinical characteristics and follow-up of thrombosis of pediatric patients with systemic lupus erythematosus (SLE).Methods:In this retrospective study, inpatients who were diagnosed in Beijing Children's Hospital with SLE complicated with arterial or venous thrombosis from January 2006 to December 2019 were collected, the clinical characteristics and outcomes were analyzed. Statistical product and Service solutions (SPSS) 25.0 was used for statistical analysis. T test or χ2 test (counting data) was used to compare the differences between groups, and Kaplan-Meier survival curve was used to analyze the time of thrombus endpoint events in lupus children. Results:A total of 1 395 newly diagnosed SLE patients were admitted. Twenty-seven cases were diagnosed with thrombosis, accounting for 1.9% of all the lupus patients. The median course from diagnosis to thrombosis was 20 days (49 days before diagnosis to 1 year after dia-gnosis). Among the 27 patients, 22(81%) cases had renal involvement. The mean SLE disease activity index (SLEDAI) score was (14±6) and (11±4) at the diagnosis of lupus and at onset of thrombosis, respectively ( t=2.547, P=0.017). 30% (8/27) of the patients had no apparent clinical manifestations of thrombosis. The patients received standard anticoagulant therapy after the diagnosis of thrombosis. During follow-up, 6 patients stopped taking medications due to the severity of the primary disease. Twenty-one patients were followed up regularly for 1-3 years. Thrombosis disappeared in 12 cases (44%), thrombolysis time ranged from 16 days to 1 year. Thrombosis were getting smaller in 9 cases (33%). And the disease was stable during follow up. Conclusion:Thrombosis is not rare in pediatric patients with systemic lupus erythematosus patients. Some patients do not have apparent clinical manifestations related to thrombus. Pediatricians should be alert to patients with renal involvement need to be more vigilant for thrombosis. Early detection and active treatment are the keys to improve the prognosis of thrombosis in pediatric SLE patients.

Objective To explore the gene mutation,clinical phenotype,treatment and prognosis of chronic infantile neurologic,cutaneous,articular (CINCA) syndrome,so as to improve the diagnosis rate,reduce the disability rate and teratogenicity rate of CINCA syndrome.Methods Ten children with CINCA syndrome admitted to our hospital were retrospectively analyzed in terms of the clinical phenotypes,auxiliary examinations,treatment and follow-up.Three ml ethylene diamine tetraacetic acid (EDTA) anticoagul-ation was taken from children and their parents with the consents.Genomic DNA was extracted by QIAamp whole blood Deoxynbonucleic acid (DNA) extraction kit (German Qiagen Company).The whole exons were detected by Agilent liquid phase capture technology (Agilent Company).Finally,Sanger sequencing was used to verify the results.Results In this study,eight mutations of NLRP3 gene were found in children with CINCA syndrome,namely 913G/A (D305N),1057G/T(V353L),1702T/A (F568I),1703T/A (F568Y),1710G/C (K570N),1789A/G (S597G),1991T/C (M664T),2269G/A (G757R).The onset age of most of the cases was less than half a month,and the initial manifestation was mainly urticaria-like rash.Short stature and special face could be seen in all 10 cases.All the patients had fever and urticarial rash in varying degrees during the course of the disease.Nine of them had obvious arthritis.Nine children had central nervous system involvement.There were 8 cases of binaural nervous deafness,7 cases of binocular optic neuritis,and 6 cases of hepato-splenomegaly and/or lymphadenopathy.Amyloid A was significantly increased.Glucocorticoids and immunosup-pressive agents are the basic drugs for the treatment of this disease.If the curative effect was not good,biological agents should be added early to alleviate the disease.Conclusion CINCA syndrome is a rare autosomal dominant hereditary disease,the main clinical manifestations of which are skin,joint and central nervous system involvement,and even amyloidosis of organs.Early diagnosis and active treatment can reduce the involvement of important organs.

Objective:To demonstrate the clinical significance of group A streptococcal infection (GAS) in patients with enthesitis related arthritis (ERA).Methods:A retrospective study was conducted on ERA (136) and PolyRF-/Oligo juvenile idiopathic arthritis (JIA) (272) patients in Beijing Children's Hospital from 2016 to 2018. Anti-streptococcal hemolysin "O" (ASO) was tested and documented in all patients. The infection rate of GAS was compared between patients with ERA and PolyRF-/Oligo JIA. Patients with ERA were divided to two groups according to the result of ASO (ASO positive and ASO negative). All the clinical data were documented and compared within the two groups. The statistical methods used mainly include t test, rank sum test, chi-square test, and Spearman correlation analysis.Results:The GAS infection rate of patients with ERA was higher than patients with PolyRF-/Oligo JIA (17.6% vs 9.5%, χ2=5.52, P=0.019). In ERA patients, clinical data were analyzed, and a statistical significant difference was observed in the presence of human leukocyte antigen (HLA)-B27 between ASO positive and ASO negative group [75.0%(18/24) vs 49.1%(55/112), χ2=5.329, P=0.021]. Statistical differences were found in Patrick's sign positive rate between the two groups [100%(24/24) vs 67.0%(75/112), χ2=10.61, P=0.001]. There was statistically significant difference between the two groups regarding the radiogr-aphic grading at the sacroiliac joint. More patients with positive ASO had grade Ⅲ damage at the sacroiliac joint compare to patients with negative ASO [68.2%(15/22) vs 28.4%(29/102), χ2=12.49, P<0.001]. The logarithmic of the ASO was slightly correlated with the radiographic grade of sacroiliac joint ( r=0.26, P=0.005). Conclusion:Patients with ERA are prone to be infected by GAS. It's probably related to HLA-B27 postivity for antigen presentation. Patients who were infected by GAS fre-quently have sacroiliac joint involvement, and tend to be more sever. This indicates that GAS may play an important role in the pathogenesis of sacroiliac joint destruction.

Objective:To explore the correlation between autoantibodies and organ involvement in children with systemic lupus erythematosus (SLE).Methods:From June 2006 to October 2020, 581 children with SLE who were hospitalized in Beijing Children's Hospital for the first time and had autoantibody detection and clinical data in our hospital were selected. A correlation study was carried out on the clinical manifestations and autoantibodies. Data were analyzed with Pearson χ2 or Fisher's exact test. P<0.05 was considered statistically significant. Results:A total of 581 children with SLE were included in this study, with a male to female ratio of 1∶3.6. The average age at diagnosis was (10.6±2.8) years, and the main symptoms were rash (388, 66.8%), fever (335, 57.7%), and joint swelling and pain (170, 29.3%). The most commonly affected organ is the blood system (414, 71.3%), followed by lupus nephritis (257, 44.2%) and arthritis (170, 29.3%). In this study, the positive rate of ANA was 100%, and the positive rates of anti-dsDNA antibody and anti-Sm antibody were 59.7% and 21.2%, respectively. The children with anti-dsDNA antibody positive were more likely to have fever (64.6% vs 47.4%, χ2=16.77, P<0.001), and the kidneys (53.3% vs 30.8%, χ2=28.80, P<0.001) and blood systems (76.1% vs 64.1%, χ2=9.79, P=0.002) were more likely to be involved than anti-dsDNA antibody negative. The proportion of renal involvement (27.8% vs 47.5%, χ2=12.69, P<0.001), blood system (57.7% vs 74.0%, χ2=10.40, P=0.001), lung involvement (12.4% vs 21.1%, χ2=3.88, P=0.049) and cardiac involvement (9.3% vs 17.8%, χ2=4.11, P=0.042) in patients with anti-SSB antibody positive were lower than those in patients with anti-SSB antibody negative. Anti-histone antibody-positive patients were prone to lupus nephritis (56.9% vs 36.6%, χ2=22.62, P<0.001), arthritis (37.6% vs 24.2%, χ2=11.77, P=0.001) and lung involvement (24.3% vs 16.8%, χ2=4.87, P=0.027). Anti-Sm antibody positive patients were prone to skin manifestations such as butterfly erythema (52.8% vs 31.7%, χ2=11.38, P<0.001) and sunlight allergy (13.8% vs 7.4%, χ2=4.96, P=0.026), but the proportion of joint involvement (22.0% vs 31.2%, χ2=4.03, P=0.045) and thrombocytopenia (17.1% vs 27.3%, χ2=5.38, P=0.026) were lower than those of anti-Sm antibody negative. Arthritis (44.4% vs 24.8%, χ2=19.00, P<0.001), secondary SS (28.6% vs 5.4%, χ2=57.98, P<0.001) and parotid gland involvement (25.6% vs 2.9%, χ2=70.84, P<0.001) were more common in RF factor positive children, but the proportion of kidney involvement (30.8% vs 48.2%, χ2=12.57, P<0.001) was lower than in RF negative children. Conclusion:The clinical manifestations of childhood SLE are diverse and highly heter-ogeneous. A variety of autoantibodies are associated with organ involvement and clinical phenotypes, and anti-SSB antibodies may have protective effects in kidney and other organ damage.