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Objective:To analyze the clinical characteristics of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).Methods:A retrospective study was conducted on AAV patients with long-term follow-up in the rheumatology outpatient clinic of Peking Union Medical College Hospital between February 2015 and February 2022. The demographic characteristics, clinical manifestations, concurrent events, treatment, and prognosis of the three clinical subtypes of AAV were collected and analyzed.Results:There were 71, 45, and 31 cases of granulomatous polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatous polyangiitis (EGPA), respectively, among 147 patients. The ANCA positivity rates in the three groups were 91.5%, 95.6%, and 19.4% ( χ2=76.68, P<0.01), respectively. The upper respiratory tract and lungs were the most frequently affected organs in GPA and EGPA, and the kidneys and lower respiratory tract were the main organs involved in MPA. In addition, cardiac and neurological involvement and thrombosis rates were significantly higher in EGPA patients than in GPA and MPA (12.9%, 9.7%, 41.9% and 19.4%, respectively; χ2=8.51、7.13、7.54、0.02, P<0.05) .The median follow-up time for the three groups of patients was 43, 28, and 46 months respectively.Relapse was more common in patients with GPA and EGPA (up to 59.2% and 64.5%; χ2=11.26, P=0.004), with the lungs and ENT being the most common relapse organs (GPA of 61.9% and 40.5%, EGPA of 55.0% and 50.0%), the lungs and kidneys were the most common manifestations in MPA relapse (64.3% and 60.0%, respectively). The main therapeutic agents were glucocortoid (95.9%), cyclophosphamide (71.4%), methotrexate (54.4%), tripterygium wilfordiz (34.0%),mycophenolate mofetil (31.3%), azathioprine (29.3%), leflunomide (19.0%), rituximab (19.0%), and tacrolimus/cyclosporine (8.8%). There were 6 deaths (4.1%) occurred during the follow-up period of this study. Conclusion:The clinical features of AAV are similar to those reported in the literature and relapses are common>he vast majority of patients need to be treated with glucocorticoid combined with immunosuppressive agents.
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Objective:To evaluate the efficacy and safety of rituximab(RTX) as remission-mainten-ance therapy in antineutrophil cytoplasmic antibody(ANCA) associated vasculitis(AAV).Methods:Patients with AAV, including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), treated with rituximab (RTX) in Peking Union Medical College Hospital during September 2005 to June 2021 were included into this study. Clinical data, relapse rate, time of first relapse and adverse events were collected and analyzed. The cumulative relapse rate was calculated by Kaplan-Meier, t test, and Man-Whithey U test and chi-square were used to compare differences between two groups. Results:① Thirty-nine AAV patients were enrolled, including 36 GPA and 3 MPA. During the 20(3, 104) months follow-up, 59.0%(23/39) patients had suffered relapses. The time for first relapse was 11(3, 42) months after remission. ② There were no difference in the relapse rate [60.0%(18/30) vs 55.6%(5/9), χ2=0.06, P=1.000), the time of first relapse [15(3, 42) vs 10(9, 30), Z=0.45, P=0.678], CD19 + B [23.5 (5, 148) cell/μl vs 3(2, 15) cell/μl, Z=0.57, P=0.605] and serum IgG [7.09(5.13, 13.90) g/L vs 9.72(5.32, 12.0) g/L, Z=0.36, P=0.770] between standard dose and low-dose groups. The rate of major relapse-free was significantly less in patients treated with standard dose than patients with reduced dose of RTX {87.1%[95% CI(73.4%, 100.8R%)] vs 64.3%[95% CI(23.1%, 105.4%)], χ2=7.59, P=0.006}. ③ There were no difference in relapse rate [50.0%(3/6) vs 60.6%(20/33), χ2=0.24, P=0.674], time of first relapse [23(6, 25) vs 11(3, 42), Z=0.05, P=0.982], CD19 + B[35(15, 50) cell/μl vs 10(0, 148) cell/μl, Z=0.95, P=0.382] and serum IgG[6.70(5.91, 7.49) g/L vs 7.69(3.78, 13.90) g/L, Z=0.48, P=0.700] between the fixed interval dosage and the on-demand dosage groups. There was no difference in the rate of major relapse-free between the two groups (100% vs 77.8%, χ2=1.79, P=0.181). ④ The incidence of infusion reaction was 5.1%(2/39) and infection was 20.5%(8/39). Serum IgG level was 4.37(3.78, 13.4) g/L at infection. There was no difference in safety between the standard and low-dose groups or between fixed interval and on-demand dosage groups ( P>0.05). Conclusion:There is no significant difference in relapse rate bet-ween the standard RTX dose and low-dose RTX induction therapy group, but the major relapse rate is sign-ificantly reduced in the standard dose RTX therapy. The relapse rate of fixed intervals dosage group is similar to that of on-demand dosage group. The safety profile of the standard dose and low-dose induction therapy groups or fixed intervals and on-demand dosage groups is similiar.
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One 51 years old man was admitted to the rheumatology department with a history of prominent eyes, headache and blurred vision for half year. The main manifestations included retrobulbar inflammatory pseudotumor and retroperitoneal fibrosis. He was initially diagnosed as granulomatosis with polyangiitis. Prednisone and cyclophosphamide were administrated and effective. New mass of dura mater and osteosclerosis presented during follow up. Finally Erdheim Chester disease(ECD) was diagnosed by biopsy and pathological examination. Vemurafenib, a v-raf murine sarcoma viral oncogenes homolog B1 (BRAF) inhibitor, 480 mg was given twice a day. The patient′s condition is stable and still in follow-up. Although ECD is a rare histiocytosis, clinicians should pay attention to its manifestations and differential diagnoses.
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Objective:To analyze the clinical and prognostic characteristics in patients with eosinophilic granulomatosis with polyangitis (EGPA).Methods:The clinical data of 146 EGPA patients hospitalized in Peking Union Medical College Hospital from 2000 to 2019 were analyzed retrospectively, including clinical manifestations, laboratory results, treatment, complications and outcome at discharge. Birmingham Vasculitis activity score-V3 (BVAS-V3) was used to evaluate disease activity.Results:The ratio of male to female was 1.8∶1 with average age (41.7±16.1) year-old. The median time from disease onset to diagnosis was 18(6, 60) months (0.5~450). The most common clinical manifestations were lung [121(82.9%)] and nose/paranasal sinuses [119(81.5%)] involvement. The positive rate of anti-neutrophil cytoplasmic antibody (ANCA) was 24.7%, mainly peripheral (P)-ANCA/myeloperoxidase (MPO)-ANCA. Compared with ANCA-negative patients, the ANCA-positive patients had a higher incidence of renal involvement and nervous system involvement (66.7% vs. 20.9%, 80.6% vs. 51.8%, P<0.001), fever and optic neuropathy (66.7% vs. 40.9%,8.3% vs. 0, P<0.05), more active disease [median BVAS-V3 25(18,30)vs. 19(14,24), P=0.001] and more elevated erythrocyte sedimentation rate [40.5(20.5,82.8)mm/1h vs. 25.0(13.3,50.8)mm/1h, P=0.006] and C-reactive protein [37.1(11.8,72.9)mg/L vs.13.5(3.4,66.1)mg/L, P=0.036]. More ANCA-negative patients had pleural effusion (20.9% vs. 5.6%, P<0.04) compared with ANCA-negative patients. Pulmonary infection was the most common complication. A total of 12 EGPA patients (8.2%)achieved remission and 6 patients (4.1%)died or discharged themselves from the hospital. Conclusion:EGPA is a rare small vessel vasculitis. The clinical manifestations and outcomes are heterogenous. The mortality rate of EGPA is high.
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Objective:To explore the efficacy and safety of anti-tumor necrosis factor alpha (TNFα) monoclonal antibodies (mAbs) for severe/refractory vasculo-Behcet′s disease (BD).Method:The clinical data of severe/refractory vasculo-BD patients treated with anti-TNFα mAbs were retrospectively analyzed. Response of anti TNFα mAbs was analyzed. The dosage changes of glucocorticoid, the level of erythrocyte sedimentation rate (ESR) and hypersensitive C-reactive protein (hsCRP) before and after treatment were recorded, as well as side effects.Result:Sixteen patients were enrolled. Arterial lesions were reported in 12 patients, including 9 with arterial aneurysm, 6 with arterial dilation, 2 with stenosis and 2 with occlusion. Seven patients presented venous thrombosis, including lower extremity veins ( n=6), cerebral venous sinus ( n=2) and inferior vena cava system ( n=2). Two cases had both arterial and venous involvement. Before the application of TNFα mAbs, all 16 patients failed to response to prednisone or its equivalent dose of 40 (7.5-90) mg/d in combination with cyclophosphamide, methotrexate, thalidomide or azathioprine for median 4 (0-156) months. After a mean duration of treatment for (17.1±6.5) months, 15 patients achieved complete remission and 1 patient achieved partial remission. Three patients received surgery without any postoperative complications. After using anti TNFα mAbs, the dosage of prednisone [5(0-12.5)mg/d vs. 40(7.5-90)mg/d, P<0.01], ESR [(7.3±4.6) mm/1h vs. (33.5±26.7) mm/1h, P<0.01] and hsCRP [1.9(0.2-11.4) mg/L vs. 24.3(0.4-113.9) mg/L, P<0.01] were significantly decreased. Side effects were observed in 2 patients. One developed pulmonary infection 12 months after adalimumab with conventional treatment. Another patient had allergy to infliximab then switched to adalimumab. Conclusion:In combination with corticosteroids and immunosuppressants, anti-TNF α mAbs are effective and well-tolerated in severe/refractory vasculo-BD, with a favorable steroid -sparing effect and rare postoperative complications.
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Objective To investigate the expression of programmed death receptor-1 (PD-1) in CD8+ T cells and FoxP3+CD4+ cells in patients with primary biliary cholangitis (PBC).Methods The peripheral blood and clinical data of 69 PBC patients in Peking Union Medical College Hospital and 58 health controls (HC) were collected.They were divided into initial treatment group and follow-up group according to whether they were treated or not.Patients in the treatment group were further divided into the refractory group and stable group according to treatment response.Flow cytometry was used to detect the expression of PD-1 in CDS+T cells and FoxP3+CD4+ cells.T-test and Person correlation analysis were used for data analysis.Results The PD-1 expression in peripheral blood mononuclear cells (PBMCs) of 69 PBC patients (12±9)％ was lower than that of HC (20±12)％ (t=-3.687,P＜0.01).The percentage of PD-1+ in FoxP3+ CD4+T cells was significantly increased in PBC (5.6±3.7)％ than HC (7.4±2.4)％ (t=2.048,P＜0.01).The proportion of CD8+T cells,PD-1 expression in CD8+T cells and the proportion of FoxP3+CD4+ cells weren't correlated with clinical parameters (P＞0.05).There was a negative correlation between the expression of PD-1 cells in FoxP3+CD4+ cells and GLOBE score (r=-0.307,P＜0.05).Conclusion The expression of PD-1 in peripheral CD8+T lymphocytes of PBC patients is lower than that of HC,and decreases more significantly in the refractory group.The expression of PD-1 on FoxP3+CD4+T cells is higher than that in HC,and is negatively correlated with the prognostic GLOBE score.It suggests that PD-1/PD-L1 pathway participates in the immune mechanism of PBC.
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Objective To investigate the clinical features of Takayasu's arteritis (TAK)with glomerulonephropathy and to improve physicians' understanding of this complication in patients with TAK. Methods Clinical data were retrospectively collected including manifestations, laboratory tests, image findings and treatment of 8 patients diagnosed as Takayasu's arteritis with glomerulonephropathy from January 2002 to January 2017 in Peking Union Medical College Hospital. Results Glomerulonephropathy was confirmed based on percutaneous renal biopsy. There were 6 women and 2 men. The median onset age and median disease duration were 24 (18-37) years and 42 (3-360) months, respectively. Five patients had hypertension. The 24 hour urinary protein was 0.18-14.91 g. Red blood cells and casts in urine were tested among 4 and 2 patients, respectively. Three patients had renal artery stenosis. Three patients demonstrated mesangial proliferative glomerulonephritis, two with IgA nephropathy, two with minimal change disease and one with membranoproliferative glomerulonephritis. Seven patients received glucocorticoid combined with cyclophosphamide therapy (glucocorticoid 40-60 mg/d, prednisone or equivalent; cyclophosphamide 0.4 g/week iv. or cyclophosphamide 0.1 g/d po.). Uninary blood cells removed and 24 hour urinary protein decreased from 1.65 g to 0.90 g after treatment for 12 months in one patient. The other 7 patients were missing. Conclusion Glomerulonephropathy is occasionally observed among TAK patients. Mesangial proliferative glomerulonephritis is the most common pathological subtype. Glucocorticoid combined with cyclophosphamide therapy could be an optional therapy for Takayasu's arteritis with glomerulonephropathy.
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Objective To investigate the health related quality of life score [primary biliary cholangitis (PBC)-40] in patients with PBC,and the relationship between PBC-40 and clinical presentations.Methods The PBC-40 score and clinical presentations in PBC patients (n=65) were adapted in this study.Patients were divided into the untreated group and the treated group,and the treated group was further divided into ursodesoxycholic acid (UDCA) response group and UDCA non-response group.PBC-40 scores of different groups were analyzed by t-test and the relationship between PBC-40 and clinical presentations were analyzed with Pearson's test.Results Dimensions of PBC-40 scores of this group of patients were as follows:symptoms were (15.8±4.1) points,itch was (4.9±2.8) points,atigue was (23.8±8.9) points,cognitive dysfunction score was (11.4±4.7) points,social activity score was (17.0±7.5) points,and the emotion score was (6.5±3.1) points.The untreated group had higher emotion scores than the treated group (t=2.024,P=0.045).Compared with the UDCA response group,UDCA non-response group had higher scores in cognitive,social and emotion dimension (t =2.126,2.309,2.062,respectively,P=0.039,0.025,0.045,respectively).Itch score was significantly correlated with total bilirubin (TBil),direct bilirubin (DBil),alkaline phosphatase (ALP) and total bile acid (TBA) (r=0.349,0.345,0.324,0.427,respectively,P＜0.01),while the social scores were correlated with TBil,DBil,aspartate aminotransferase (AST) and TBA (r=0.361,0.383,0.316,0.331,P＜0.01) and emotion scores were associated with ALT,TBil,GGT,ALP,AST and TBA (r=0.332,0.430,0.265,0.326,0.297,0.353,P＜0.05).ConclusionPBC-40 can be used as a health-related quality of life assessment for PBC patients inChinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health quality of life in PBC patients.Conclusion PBC-40 can be used as a health-related quality of life assessment for PBC patients in Chinese population.Itch,social and emotion dimensions are correlated with clinical activity indicators.Hyperbilirubin,ALP and TBA can predict low health related quality of life in PBC patients.
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Objective To explore the efficacy and safety of tacrolimus among Chinese Takayasu arteritis (TAK) patients. Methods This was a single center, prospective study of active TAK patients treated with tacrolimus. Clinical manifestations, white blood cell count, hemoglobin level, erythrocyte sedimentation rate (ESR), hypersensitivity C reactive protein (hsCRP), alanine and aspartate aminotransferase and serum creatinine were recorded before and during tacrolimus treatment. Vascular changes were repeated every 6 months during tacrolimus treatment. All data were analyzed by statistical product and service solutions (SPSS) 20.0 statistical software, unpaired t test and Fisher exact probability and Kruskal-Wallis H test were used for statistical analysis. Results A total of 19 consecutive patients with an average age of (26 ±6) years were analyzed in this study. Sixteen of them were women. Pulselessness, fatigue, asymmetric blood pressure and fever were the most common clinical findings. Cervical and subclavian artery were more vulnerable. The most common artery involvement pattern was Numano type Ⅰ, followed by type Ⅱa and type Ⅴ. The median tacrolimus dosage was 2(2, 3) mg. Tacrolimus was effective in 9 out of the 19 patients. Patients who responded to tacrolimus tended to have lower mean ESR [(33±29) mm/1 h vs (42±20) mm/1 h, t=-0.776, P=0.448] and hsCRP [(20 ±31) mg/L vs (54 ±45) mg/L, t=-1.758, P=0.099] levels. However, no statistical significance was observed. During tacrolimus treatment, no drug related side effect was observed. Conclusion Tacrolimus is an alternative and effective therapy for some of the TAK patients.
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Objective To study the clinical profile of patients with multicentric reticulohistiocytosis (MRH).Methods The clinical manifestations,image and histologic characteristics of ten patients with MRH were collected,and the relevant literatures were reviewed.Results Seven cases were women.The median (quartile) age was 46.5 (44.5-55.3) years.Clinical symptoms included papulonodular lesions on the skin (ten cases),erosive polyarthritis (ten cases),myositis (four cases),lung nodules (three cases),larynx nodules (one case) and serositis (one case).Biopsy demonstrated infiltration of multinucleated giant cells with CD68 positive and glassy cytoplasm.All of the ten patients were treated with corticosteroids and disease-modifying antirheumatic drugs,skin lesions of seven patients were ameliorated and arthritis was improved in three patients.Conclusion MRH is a systemic disease that has characteristic clinical manifestations and unique histological findings.Deep understanding of this disease can avcid.isdiagnose.Further studies are needed to explore effective treatment.
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Objective To investigate the clinical significance of IgG subclasses in patients with primary Sj(o)gren's syndrome (pSS) patients.Methods The serum was collected from 101 pSS patients and 40 healthy subjects.The content of IgG subclasses was determined by immuno-scatter turbidmetry.The difference of IgG subclasses distribution between pSS patients and healthy subjects was analyzed.Com-bined with the clinical information of the SS patients,the difference of IgG subclasses distribution in SS patients with different characteristics was analyzed.For group comparisons,measurement data were compared using unpaired Student's t test.Results The average levels of serum IgG1-4 in 40 healthy controls were (8085±1566) mg/L,(5406±2151) mg/L,(395±233) mg/L and (566±420) mg/L.The percentage of IgG1-4 were (56.8±8.2)％,(36.6±7.8)％,(2.7±1.5)％ and (3.9±2.8)％.The average levels of serum IgG1-4 in 101 pSS patients were (14 094±5534) mg/L,(3912±1750) mg/L,(565±565) mg/L and (404±504) mg/L,The percentage of IgG1-4 were(73.0±10.9)％,(21.7±9.8)％,(3.1±2.0)％ and (2.2±2.4)％.In pSS patients,the levels of IgG1,IgG3 and IgG1/IgG were significantly higher,while the IgG2,IgG2/IgG and IgG4/IgG levels were significantly lower,compared with those of the healthy subjects (P＜0.05).There was no significant difference in the IgG subclasses distribution between the pSS patients whose had systemic involvement and the pSS patients who did not have systemic involvement(P＞0.05).The IgG subclasses distribution was abnormal in SS patients who IgG was normal,compared with the healthy subjects.Conclusion A characteristic IgG subclasses distribution abnormality exists in pSS patients,and the production of anti-SSA (Sj(o)gren's syndrome A) antibody is associated with the increase of IgG1.However,no relationship has been found between the systemic involvement of pSS patients and the abnormal distribution of IgG subclasses.
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Objective To investigate the changes of monoamine neurotransmitters of the brain in two tat models of morphine dependence,and to explore the effects of sinomenine on morphine dependence.Methods A physical dependent rat model was established with morphine at a gradually increasing dosage and the withdrawal syndrome was scored after naloxone precipitation.The conditioned place preference(CPP)in rats induced by morphine was used to investigate psychic dependence in rots.Contents of norepinephrine(NE),dopamine(DA)and serotonin(5-HT)in hypothalamus of rats were assayed with a fluorescent method.Results 1.In naloxone precipitated withdrawal test of in morphine-dependent rats,after morphine withdrawal,the rats presented marked with drawal symptoms and signs,their withdrawal scores were significantly increased,and the levels of NE and 5-HT in hypothalamus of the rats were significantly increased than the control group Ⅰ(7.07±1.406μg/g wet tissue and 1.15±0.346 μg/g wet tissue,respectively,P<0.01),but the content of DA was markedly reduced than the control group Ⅰ(0.28±0.121 μg/g wet tissue,P<0.05).2.In CPP model,morphine caused a marked place preference in rats and the levels of DA and 5-HT in hypothalamus were significantly increased than the control group Ⅱ(1.13±0.359 μg/g wet tissue and 1.23±0.343μg wet tissue,respectively,P<0.01),but the content of NE was not significantly changed(3.28±1.098 μg/g wet tissue,P>0.05).Sinomenine could significantly inhibit the withdrawal syndrome and development of CPP induced by morphine in rats,and could suppress the rising of monoamine neurotransmitters of the brain in two morphine dependent models in rats.Conclusion In the physical dependent model induced by morphine in rats,the rising of NE and 5-HT in the rat brain were significant,but in CPP model induced by morphine in rats,the levels of DA in the rat brain were enhanced predominately.Sinomenine could inhibit the withdrawal syndrome and development of CPP in rats,and regulate and improve the function of monoamine nerve system.