Mechanism of action and clinical research progress of iguratimod in connective tissue diseases / 中国药房

As a new type of immunosuppressant，iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines， and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors，reduce the production and deposition of immune complexes in the body，and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin，Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand， and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway，tumor necrosis factor-α，interleukin-1，interleukin-6，matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue，and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis，and no obvious safety risks have been found.

Clinical Profile of Sharp Syndrome: Is it rare in India?

Background: In 1972, Dr Sharp and colleagues described a new connective tissue disease, characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis/ dermatomyositis (PM/DM) and by the presence of antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1 snRNP). This condition was termed mixed connective tissue disease (MCTD) and proposed as a distinct disease. Later, after observing the clinical evolution of MCTD patients, Sharp himself agreed that the original concept of MCTD had to be modified and that Internal organs were at risk for serious complications; patients were not always steroid responsive; prognosis was not always benign. Materials and methods: Patients in the age group of 15-50 years diagnosed to have connective tissue diseases were included. 8 patients in the age group of 15-50 admitted in Medicine department were taken and they were evaluated for the clinical profile of sharp syndrome by thorough clinical examination, routine laboratory tests and special investigations depending on the clinical profile. Results: 8 patients with connective tissue disease attending the medicine OPD were studied. Of these 8 patients were female patients. The median age of onset was 36 years, 8 patients met criteria by sharp and Alarcon-Segovia. The clinical features of patients at presentation are Raynaud抯 phenomena, Puffy fingers, esophagus dysmotility, skin rash, interstitial lung disease, arthritis, pulmonary hypertension, myositis, anemia. Conclusion: SHARP syndrome is a rare condition, as evidenced by the small series of cases reported to date. Diagnosis is based on clinical and paraclinical criteria. The evolution can be interspersed with various complications that can affect the short, medium and long-term prognosis

Analysis of pregnancy outcomes, disease progression, and risk factors in patients with undifferentiated connective tissue disease / 北京大学学报(医学版)

OBJECTIVE@#To investigate the fetal and maternal outcomes, risk factors of disease progression and adverse pregnancy outcomes (APOs) in patients with undifferentiated connective tissue disease (UCTD).@*METHODS@#This retrospective study described the outcomes of 106 pregnancies in patients with UCTD. The patients were divided into APOs group (n=53) and non-APOs group (n=53). The APOs were defined as miscarriage, premature birth, pre-eclampsia, premature rupture of membranes (PROM), intrauterine growth restriction (IUGR), postpartum hemorrhage (PPH), and stillbirth, small for gestational age infant (SGA), low birth weight infant (LBW) and birth defects. The differences in clinical manifestations, laboratory data and pregnancy outcomes between the two groups were compared. Logistic regression analysis was performed to analyze the risk factors for APOs and the progression of UCTD to definitive CTD.@*RESULTS@#There were 99 (93.39%) live births, 4 (3.77%) stillbirths and 3 (2.83%) miscarriage, 20 (18.86%) preterm delivery, 6 (5.66%) SGA, 17 (16.03%) LBW, 11 (10.37%) pre-eclampsia, 7 (6.60%) cases IUGR, 19 (17.92%) cases PROM, 10 (9.43%) cases PPH. Compared with the patients without APOs, the patients with APOs had a higher positive rate of anti-SSA antibodies (73.58% vs. 54.71%, P=0.036), higher rate of leukopenia (15.09% vs. 3.77%, P=0.046), lower haemoglobin level [109.00 (99.50, 118.00) g/L vs. 124.00 (111.50, 132.00) g/L, P < 0.001].Multivariate Logistic regression analysis showed that leucopenia (OR=0.82, 95%CI: 0.688-0.994) was an independent risk factors for APOs in UCTD (P=0.042). Within a mean follow-up time of 5.00 (3.00, 7.00) years, the rate of disease progression to a definite CTD was 14.15%, including 8 (7.54%) Sjögren's syndrome, 4 (3.77%) systemic lupus erythematosus (SLE), 4 (3.77%) rheumatoid arthritis and 1 (0.94%) mixed connective tissue disease. Multivariate Cox proportional risk regression analysis showed that Raynaud phenomenon (HR=40.157, 95%CI: 3.172-508.326) was an independent risk factor for progression to SLE.@*CONCLUSION@#Leukopenia is an independent risk factor for the development of APOs in patients with UCTD. Raynaud's phenmon is a risk factor for the progression of SLE. Tight disease monitoring and regular follow-up are the key measures to prevent adverse pregnancy outcomes and predict disease progression in UCTD patients with pregnancy.

Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum / 北京大学学报(医学版)

OBJECTIVE@#To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum.@*METHODS@#We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness.@*RESULTS@#A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05).@*CONCLUSION@#The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.

Three years follow-up report of two diffuse connective tissue disease cases caused by SARS-CoV-2 infection / 中国热带医学

@#Abstract: To report on two patients with Coronavirus Disease 2019 (COVID-19) combined with diffuse connective tissue disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection followed for nearly 3 years, in order to understand the long-term effects on the patients' immune system. Both patients were male, aged 81-82 years, and were hospitalized with fever on January 29, 2020 and February 10, 2020, respectively. Both were diagnosed with COVID-19 after positive SARS-CoV-2 polymerase chain reaction (PCR) tests. After receiving anti-infection treatment, cough suppressants, ex‐pectorants, and symptomatic supportive treatment, their body temperature returned to normal and two consecutive PCR tests were negative for SARS-CoV-2, and they were discharged from hospital. However, due to recurring fevers and varying degrees of rheumatic disease-related symptoms, both patients were readmitted to the hospital, indicating the presence of positive auto‐ antibodies and organ involvement. One patient recovered from COVID-19 with recurrent fever, joint pain, muscle aches and subcutaneous nodules, and was subsequently diagnosed with undifferentiated connective tissue disease. The other patient developed recurrent fever, mouth ulcers and rash after recovery from COVID-19 and was subsequently diagnosed with anti neutro phil cytoplasm antibody (ANCA)-associated vasculitis (AAV). The patient was treated with glucocorticoids and immunosuppres sive drugs and the symptoms resolved rapidly and subsequent laboratory and imaging examinations showed stable condition. However, due to self-termination of medication, their symptoms quickly relapsed, and further treatment with glucocorticoids and immunosuppressive agents resulted in sustained stability of their condition. The erythrocyte sedimentation rate and hyper‐sensitive C-reactive protein remained within normal limits, and lung CT scans showed stable lesions with partial absorption.SARS-CoV-2 infection may have long-term effects on patients' immune systems, leading to abnormal immune responses and diffuse connective tissue disease. This suggests that regular follow-up observation of immune system-related diseases may be necessary for elderly patients with COVID-19.

Clinical Profile of Connective Tissue Disease- related Interstitial Lung Diseases at a Tertiary Care Center in Western India

Connective tissue disorders (CTDs) are one of the common causes of interstitial lung diseases (ILDs). This prospective observational study included around 51 patients of CTD-ILDs, and their demographic, clinical, radiological, and laboratory profiles were studied. The most common type of CTD-ILD in our study is rheumatoid arthritis-related ILD. On high-resolution computed tomography (HRCT) thorax, nonspecific interstitial pneumonia (NSIP) was the most common pattern seen in 30 patients (59%), followed by usual interstitial pneumonia (UIP) seen in 20 patients (39%). Even though CTD-ILDs are similar to other idiopathic ILDs in clinical and radiological presentation, patients with CTDs have to be evaluated clinically and radiologically for early diagnosis. Early treatment initiation and pulmonary rehabilitation help in delaying the progression of disease. Among all ILDs, CTD-ILDs are associated with better prognosis and survival

Pulmonary Hypertension Registry of Kerala, India (PRO-KERALA): One-year outcomes

Background: Short term outcomes of patients with pulmonary hypertension are not available from low and middle-income countries including India. Methods: We conducted a prospective study of 2003 patients with pulmonary hypertension, from 50 centres (PROKERALA) in Kerala, who were followed up for one year. Pulmonary hypertension (PH) was mainly diagnosed on the basis of Doppler echocardiography. The primary outcome was a composite endpoint of all-cause death and hospital admission for heart failure. All cause hospitalisation events constituted the secondary outcome. Results: Mean age of study population was 56 ± 16 years. Group 1 and Group 2 PH categories constituted 21.2% and 59% of the study population, respectively. Nearly two-thirds (65%) of the study participants had functional class II symptoms. 31% of Group 1 PH patients were on specific vasodilator drugs.In total, 83 patients (4.1%) died during the one-year follow-up period. Further, 1235 re-hospitalisation events (61.7%) were reported. In the multivariate model, baseline NYHA class III/IV (OR 1.87, 95% C.I. 1.35e2.56), use of calcium channel blockers (OR 0.18, 95% C.I. 0.04e0.77), vasodilator therapy (OR 0.5, 95% C.I. 0.28e0.87) and antiplatelet agents (OR 1.80, 95% C.I. 1.29e2.51) were associated with primary composite outcome at one-year (p < 0.05). Conclusion: In the PROKERALA registry, annual mortality rate was 4%. More than half of the patients reported re-hospitalisation events on follow up. Uptake of guideline directed therapies were suboptima

Serum MMP-9, SP-D, and VEGF levels reflect the severity of connective tissue disease-associated interstitial lung diseases

Abstract Background: Interstitial lung disease (ILD) is a common pulmonary complication of connective tissue disease (CTD). This study aims to evaluate the clinical diagnostic value of matrix metalloproteinase-9 (MMP-9), surfactant protein-D (SP-D), and vascular endothelial growth factor (VEGF) as potential biomarkers for CTD-ILD. Methods: This research included 33 CTD-ILD patients, 31 CTD patients without ILD, and 24 healthy control subjects. Then, the value of biomarkers for the diagnosis and evaluation of CTD-ILD was assessed through high-resolution computed tomography (HRCT) findings and pulmonary function test (PFT) parameters. Results: The serum MMP-9, SP-D, and VEGF levels in the CTD-ILD group were higher than those in the CTD-NILD group and healthy group. The ROC curve indicates that VEGF has good to excellent diagnostic performance in diagnosing CTD-ILD, the cut-off that best optimizes sensitivity and specificity in diagnosing CTD-ILD is 277.60 pg/ml (sensitivity, 87.9%; specificity, 83.6%), with an area under the curve (AUC) of 0.905 (95% confidence interval (CI) 0.842-0.968); The ROC curve for MMP-9 suggests this biomarker is fair for diagnosis of CTD-ILD(sensitivity, 81.8%; specificity, 81.8%), with an AUC of 0.867 (95% CI 0.784-0.950), but SP-D only provided lower specificity with higher sensitivity in diagnosing CTD-ILD(sensitivity, 90.9%; specificity, 40.0%). The different serum biomarkers are more specific and sensitive when combined to diagnose ILD. The semiquantitative score for the degree of ILD severity on HRCT was positively correlated with SP-D and VEGF levels ( r = 0.461, P = 0.007; r = 0.362, P = 0.039), and serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. The percentage of diffusing capacity of the lung for carbon monoxide (DLco) (% predicted) had a negative correlation with the SP-D level ( r = − 0.407, P = 0.044) and a statistically negative correlation between MMP-9 and the forced vital capacity (FVC) ( r = − 0.451, P = 0.024). Conclusions: Serum MMP-9, SP-D, and VEGF levels may have clinical value in screening and evaluating the severity of CTD-ILD. Key points Serum MMP-9, SP-D, and VEGF levels were increased in patients with CTD-ILD and they may have clinical value in screening and evaluating the severity of CTD-ILD. Serum SP-D and VEGF levels had a positive correlation with ILD severity as measured using semiquantitative HRCT scores. Serum MMP-9 levels were elevated in the UIP subgroup compared to the non-UIP subgroup. Therefore, further research is required to determine the role of serum MMP-9 levels in the preliminary determination of the ILD subtype. Serum MMP-9 levels had a negative correlation with DLco, and serum SP-D levels had a negative correlation with FVC.

Clinical analysis of 53 children with connective tissue disease complicated with interstitial lung disease / 中华实用儿科临床杂志

Objective:To investigate the clinical manifestations, characteristics of chest high-resolution computed tomography (HRCT), and prognosis of connective tissue disease (CTD) complicated with interstitial lung disease (ILD) in children.Methods:The clinical data of 53 children with CTD-ILD who were admitted to the Department of Rheumatology and Immunology, Affiliated Xi′an Children′s Hospital of Xi′an Jiaotong University from October 2013 to October 2019 were retrospectively analyzed, including clinical manifestations, blood gas analysis, chest HRCT and prognosis.Results:As for these 53 children with CTD-ILD, the ratio of male to female was 1.0∶1.4, the average age was (7.50±3.34) years, and the course of disease was 2.00 (0.85, 7.50) months.Among them, there were 25 cases (47.2%) of juvenile idiopathic arthritis (JIA), 15 cases (28.3%) of systemic lupus erythematosus (SLE), 11 cases of polymyositis / dermatomyositis (PM/DM) (20.7%), 1 case of overlap syndrome (OS) (1.9%), and 1 case of allergic granulomatosis with polyangiitis (AGPA) (1.9%). Although cough (39.6%) was the most common symptom of respiratory system in these children with CTD-ILD and fever(66.0%) was the most common symptom in the systemic features.Blood gas analysis appeared abnormal in 17 cases, including 10 cases of hypoxemia (18.9%) and 7 cases of type Ⅰ respiratory failure (13.2%). HRCT chest showed ground glass shadow, strip shadow, subpleural spot shadow, grid shadow, pleural thickening, consolidation shadow, nodular shadow and cystic low-density shadow, with the proportion of 52.8%, 26.4%, 22.6%, 18.9%, 11.3%, 7.5%, 1.9% and 1.9%, respectively; nonspecific interstitial pneumonia (NSIP)(39.6%) was the most common type of imaging classification.After the combined treatment with glucocorticoids, immunosuppressive agents and biological agents, HRCT chest showed remarkably improvement in 36 cases (67.9%), while no change in 8 cases (15.1%). A total of 75.0%(33 cases) of 44 cases were infected in the course of combined treatment.In addition, 9 cases (17.0%) died from acute respiratory distress syndrome (ARDS), among which 4 cases exacerbated to rapid progressive luge disease and 5 cases aggravated secondary ARDS due to infection.Conclusions:Only a small number of children with CTD-ILD have respiratory symptoms and signs.HRCT chest contributes to the early diagnosis of CTD-ILD, and its imaging manifestations are diverse.Blood gas analysis and HRCT chest play an important role in the disease evaluation and treatment planning.Moreover, it is the direction for further research to develop effective methods to prevent and control secondary infection so as to improve the survival rate and reduce the mortality rate during the active treatment of primary diseases.

Standardized diagnosis and treatment of undifferentiated connective tissue disease and mixed connective tissue disease / 中华内科杂志

Undifferentiated connective tissue disease (CTD) usually refers to patients who are presented with certain symptoms and signs related to CTD, and positive serological evidence of autoimmune diseases but don′t fulfill any of the classification criteria for a certain CTD. Mixed CTD refers to patients who are presented with one or more clinical manifestations such as hand swelling, synovitis, myositis, Raynaud′s phenomenon, and acrosclerosis. Patients with mixed CTD always have high-titer anti-nuclear antibodies (ANA) of speckled pattern and high-titer anti-U 1 ribonuclear protein (RNP) antibody in serum, while with negative anti-Sm antibody. The update of diagnosis and treatment of undifferentiated CTD and mixed CTD lags behind other established CTD. There is a lack of evidence from randomized controlled trials or guidelines/recommendations on the treatment of undifferentiated CTD or mixed CTD. At present, the conventional therapy is mainly adopted according to the specific clinical manifestations of the disease. The standardized diagnosis and treatment of undifferentiated CTD and mixed CTD were drafted by the Chinese Rheumatology Association based on the previous guidelines and the progress of available evidence, so as to improve the management of these patients in China.

The 498th case: rash, fever and hematuria / 中华内科杂志

A 50-year-old man was admitted to the Department of Rheumatology at Peking Union Medical College Hospital with rash for 6 months, and fever and hematuria for 5 months. The main clinical manifestations included fever, fatigue, purpura, hematuria and thrombocytopenia. He was positive for antinuclear antibody (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and rheumatoid factor (RF), and had low complement levels. Initial blood culture, echocardiography and chest CT showed no signs of infection. Diagnosis of connective tissue disease was made initially. His disease improved under treatment with glucocorticoids and immunosuppressive agents, but relapsed when glucocorticoids were tapered. After admission, the diagnosis was reconsidered, and infective endocarditis was finally diagnosed with repeated positive blood cultures and vegetations detected by transesophageal echocardiography. Amoxicillin and clavulanate potassium were initiated, and surgery was performed. His symptoms finally recovered gradually.

Clinical analysis of cryptococcosis neoformans infection in patients with connective tissue disease / 中华风湿病学杂志

Objective:To improve the level of clinical diagnosis and treatment by analyzing the clinical features and relevant factors of cryptococcosis neoformans in patients with connective tissue disease(CTD).Methods:Twelve patients with CTD and cryptococcosis neoformans infection in Peking University People's Hospital from January 2010 to April 2021 were retrospectively enrolled. Clinical and laboratory data, treatment and outcome were collected and analyzed. Independent sample t-test or Rank-sum test was used. Results:The age of the patients ranged from 18 to 85 years old(mean 51 years old), all of whom were female. None of them were exposed to pigeons and their feces. Of the 12 patients, 3 patients suffered from rheumatoid arthritis, 7 patients had systemic lupus erythematosus, 1 patient was diagnosed with primary Sj?gren 's syndrome, and 1 patient was diagnosed as undifferentiated connective tissue disease. Four cases were cryptococcal meningitis, 8 were pulmonary cryptococcosis. None of the 12 patients had immunodeficiency virus infection. All 12 patients were given glucocorticoid alone or combined with immunosuppressive or biological agents. All were detected with positive cryptococcus neoformans antigen in serum; 6 got lumbar puncture, 2 cases were positive for ink stain, cerebrospinal fluid (CSF) culture were positive in 2, in whom 3 had high intracranial pressure, in which the highest one was more than 600 mmH 2O (1 mmH 2O=0.009 8 kPa); 7 cases underwent lung biopsy. Among these patients, all were positive for cryptococcosis neoformans in lung tissue pathological examination; 6 had the number of peripheral lymphocytes less than 1.0×10 9/L, and 2 were detected for the number of CD4 + T cell, which was significantly decreased. As for the initial anti-fungal drug therapy, all cases were treated with fluconazole intravenously; 2 were treated with combined amphotericin, 1 was treated with combined fluorocytosine, 1 was treated with amphotericin and fluorocytosine. Then oral flu-conazole was prescribed as sequential therapy. The whole treatmentcourse ranged from 4 to 21 months. Eleven patients were cured, and 1 was relieved. Conclusion:Patients with connective tissue disease complicated with cryptococcus neoformans infection have atypical clinical symptoms. Treatment with immunosuppressive drugs and glucocorticoids are related causes. Patients with decreased peripheral blood lymphocytes, especially CD4 + T cell, are more susceptible to infection. Early diagnosis and timely treatment are the key to improve the prognosis and cure of the disease.

Serum 25-hydroxyvitamin D level in patients with connective tissue disease-related pulmonary arterial hypertension / 中华风湿病学杂志

Objective:To investigate the clinical significance of serum 25-hydroxyvitamin D [25(OH)D] level in patients with connective tissue disease (CTD) related-pulmonary arterial hypertension (PAH).Methods:CTD patients with PAH (CTD-PAH) and without PAH (CTD-non-PAH) were colle-cted. All data were analyzed.Results:The serum 25(OH)D in the CTD-PAH group was significantly lower than that in the CTD-non-PAH group [(14±8) ng/ml vs (20±8) ng/ml, t=-5.94, P<0.001]. The 25(OH)D deficiency rate in the CTD-PAH group 86.2%(112/130) was significantly higher than that in the CTD-non-PAH group 57.7% (75/130) ( χ2=26.07, P<0.001), while the insufficiency rate was significantly lower [10.0%(13/130) vs 32.3% (42/130), χ2=19.39, P<0.001]. Serum 25(OH)D levels in the systemic lupus erythematosus (SLE), systemic sclerosis (SSc) associated PAH group were lower than those in the SLE [14(8, 17) ng/ml vs 19(15, 23) ng/ml, Z=-3.66, P<0.001], SSc [11(8, 17) ng/ml vs 24(18, 30) ng/ml, Z=-4.97, P<0.001] without PAH group. The levels of serum 25(OH)D in CTD-PAH youthful group, in the middle age group were lower than that in CTD-non-PAH youthful group [(12±8) ng/ml vs (19±8) ng/ml, t=-4.36, P<0.001] and in the middle age group [(14±7) ng/ml vs (21±8) ng/ml, t=-3.75, P<0.001]. Serum levels of 25(OH)D [ OR (95% CI)=1.100 (1.058, 1.144), P<0.001], uric acid [ OR(95% CI)=0.996(0.993, 0.998), P=0.003], immune globulin (Ig)G [ OR(95% CI)=1.123(1.057, 1.194), P<0.001] were associated with PAH in CTD patients. Serum 25(OH)D was positively correlated with calcium ( r=0.24, P=0.007), while negatively correlated between serum 25(OH)D and IgM ( r=-0.34, P<0.001). Conclusion:The occurrence and development of CTD-PAH may be related to the decrease of 25(OH)D level. Serum 25(OH)D level is associated with PAH in CTD patients.

Clinical Trial of Buyang Huanwutang in Treatment of Connective Tissue Disease-associated Pulmonary Fibrosis with Syndrome of Qi Deficiency and Blood Stasis / 中国实验方剂学杂志

ObjectiveTo evaluate the effect and safety of Buyang Huanwutang in treatment of connective tissue disease-associated pulmonary fibrosis in the patients with syndrome of Qi deficiency and blood stasis and explore the possible anti-fibrosis mechanism of Buyang Huanwutang. MethodSixty-six patients with connective tissue disease-associated pulmonary fibrosis with syndrome of Qi deficiency and blood stasis were randomized to receive either Buyang Huanwutang combined with routine therapy or routine therapy for 4 weeks. The primary outcome indicator was change in forced vital capacity （FVC） from the baseline， and the secondary outcome indicators included the changes in percentage of predicted forced vital capacity （FVC%pred）， percentage of forced expiratory volume in first second to predicted value （FEV1%pred）， King's Brief Interstitial Lung Disease （K-BILD） total score， 6 minute walking distance （6MWD）， hydroxyproline （HYP）， matrix metalloproteinase （MMP）， tissue inhibitor of metalloproteinase-1 （TIMP-1）， and transforming growth factor-β （TGF-β） from baseline. Patients in line with the inclusion criteria were included in the primary analysis， and sensitivity analysis was performed after multiple imputation of missing data. Safety set was adopted for safety analysis. ResultThe 66 patients （included in the sensitivity analysis） meeting the inclusion criteria included 34 in the observation group and 32 in the control group， and 60 patients finally received the whole trial intervention （included for primary analysis）. Compared with the baseline， the FVC increased in the observation group and decreased in the control group after intervention （P<0.01）， which was consistent between the sensitivity analysis and the primary analysis. The changes in FVC%pred， FEV1%pred， 6MWD， and K-BILD total score from baseline in the observation group were superior to those in the control group （P<0.01）， with consistent results between the sensitivity analysis and the primary analysis. TIMP-1 in the observation group decreased compared with baseline （P<0.05）， while TIMP-1 in the two groups showed no significant changes from the baseline The observation group outperformed the control group in the changes in HYP， MMP-9， and TGF-β from baseline （P<0.05）. The common adverse events were cough， diarrhea， nausea， rash， and upper gastrointestinal tract infection， the incidence of which showed no statistical difference between the two groups. ConclusionBuyang Huanwutang can improve lung function， motor function， and quality of life in patients with connective tissue disease-associated pulmonary fibrosis and has good safety. The mechanism may be related to the reduction of TGF-β， MMP-9， and TIMP-1 levels and maintaining of MMP-9/TIMP-1 balance.

Enfermedad indiferenciada del tejido conectivo con progresión a esclerosis sistémica / Undifferentiated disease of the connective tissue with progression to systemic sclerosis

La enfermedad indiferenciada del tejido conectivo es una condición de etiología desconocida que comparte características clínicas, patológicas y de laboratorio de varias colagenosis, sin cumplir los criterios del Colegio Americano de Reumatología para el diagnóstico de una enfermedad reumática específica y muchos pacientes evolucionan a condiciones definidas a lo largo del tiempo tales como Lupus, Esclerosis sistémica progresiva, Enfermedad de Sjögren entre otros. Antecedentes: Linfoma Hodgkin diagnosticado desde 2012 para lo cual recibió múltiples esquemas de quimioterapia. Las muestras de ganglio y médula ósea se habían enviado al laboratorio de Inmunopatologia de la Universidad de Stanford y allí no se apreciaron hallazgos compatibles con enfermedad linfoproliferativa. Enfermedad actual: Mujer de 27 años de edad con cuadro clínico de 1 mes de evolución, caracterizado por edema blando en miembros inferiores acompañado de edema palpebral matutino; concomitantemente presenta aumento de temperatura intermitente sin patrón especifico y dolor osteomuscular generalizado con limitación para la deambulación. Se ingresa. Al examen físico, regulares condiciones clínicas. En la piel se aprecia engrosamiento cutáneo importante. Se realizó biopsia cutánea y los hallazgos fueron compatibles con Esclerosis Sistémica(AU)

Undifferentiated connective tissue disease is a condition of unknown etiology that shares clinical, pathological and laboratory characteristics of several collagenopathies that do not meet the criteria of the American College of Rheumatology for the diagnosis of a specific disease; a large number of patients evolve to conditions defined over time such as Lupus, Systemic Sclerosis, Sjogren's Disease, among others. Past history: Hodgkin lymphoma was diagnosed since 2012 for which she received multiple chemotherapy schemes. A gland biopsy was sent to the Stanford University, as well as a bone marrow sample, and lymphoma was discarded. Present history: this 27-year-old female consulted for edema in lower limbs present during one month, accompanied by eyelid edema in the mornings; also fever without a specific pattern, myalgias and arthralgias. On physical examination, the skin was thickened and limb edema was present. A skin biopsy was performed, and the findings were consistent with Systemic Sclerosis. The patient is receiving cyclophosphamide and Azathioprine and leading her normal life(AU)

A Mother-Son Case of Non-Marfan Syndrome with Acute Aortic Dissection on the Same Day / 日本心臓血管外科学会雑誌

It is well known that Marfan syndrome is a genetic disorder characterized by congenital abnormality of connective tissue, in which the associated prognosis is affected by aortic lesions, and in particular the onset of aortic dissection, with some reports of familial aortic dissection. Meanwhile, it has been reported that in the absence of genetic disorder, aortic dissection occurring in two or more individuals within a family is rare. We experienced a mother-son case of non-Marfan syndrome that developed aortic dissection on the same day, and thus report our findings. Case 1 (son) was a 32-year-old man with no particular medical history observed. He had experienced epigastric pain in the early morning and come to the emergency room in our hospital, where contrast-enhanced computed tomography (CT) led to diagnosis of acute aortic dissection (Stanford type B). He was admitted to the intensive care unit, and received treatment by anti-hypertensive therapy. Case 2 (mother) was a 61-year-old woman who was prescribed internal medicines for hypertension. She had been informed that her son was hospitalized for aortic dissection, and had visited the hospital to see him. While visiting her son in the hospital room, she developed sudden chest pain and remarkable cold sweats, and upon undergoing contrast-enhanced CT, she was diagnosed with acute aortic dissection (Stanford type A). Then emergency hemiarch replacement was performed. In the family tree, there were some cases of cerebrovascular disease found on the mother's side. Pathology findings of the aorta for the mother revealed cystic medial necrosis and genetic screening subsequently performed revealed TGFBR2 mutation. Both subjects exhibited good progress, with the son discharged from hospital after three weeks, and the mother discharged 14 days after surgery.

Efficacy of Hormone Combined with Cyclophosphamide in the Treatment of Connective Tissue Disease-associated Interstitial Lung Disease and Analysis of Its Influential Factors / 中国药房

OBJECTIVE：To investigate the efficacy of hormone combined with cyclophosphamide in the treatment of connective tissue disease-associated interstitial lung disease （CTD-ILD）and to analyze its influential factors. METHODS ：100 patients diagnosed as CTD-ILD in our hospital from Jan. 2018 to Jan. 2019 were randomly divided into observation group and control group ，with 50 cases in each group. Control group was treated with Compound cyclophosphamide tablets ，50 mg each time，3-4 times each day. Observation group was additionally treated with Prednisone acetate tablets ，10 mg each time ，3-4 times each day ，on the basis of control group. Treatment courses of 2 groups lasted for 6 months. The clinical efficacy ，the occurrence of ADR，lung function before and after treatment ，the levels of peripheral IL- 6，CRP and PCT and quality of life （SGRQ score ）were compared between 2 groups. According to the therapeutic efficacy ，all patients were divided into effective group and ineffective group. The related factors influencing the clinical efficacy of CTD-ILD were analyzed by univariate and multivariate Logistic regression analysis. RESULTS ：After treatment ，total response rate ，FVC，FEV1 and DLCO of observation group were significantly higher than those of control group ，while SGRQ score ，levels of IL- 6，CRP and PCT in peripheral blood were significantly lower than control group （P＜0.05）. There was no significant difference in the total incidence of ADR between 2 groups（P＞0.05）. Univariate analysis showed that there were no significant differences in gender ，age，past medical history and CTD type between effective group and ineffective group （P＞0.05）. However ，there were statistical significancant differences in the distribution of different levels of IL- 6，CRP and PCT in peripheral blood between 2 groups（P＜0.05）. Multivariate Logistic regression analysis showed that IL- 6 was an independent risk factor for therapeutic efficacy of combined therapy [OR （95％CI）＝ 4.537（3.668，10.352），P＝0.002]. CONCLUSIONS ：Hormone combined with cyclophosphamide can significantly improve the therapeutic efficacy of CTD-ILD patients ，improve their lung function and quality of life ，and reduce the expression level of inflammatory factors. The level of IL- 6 is an independent risk factor affecting the efficacy of the treatment ，and its changes should be paid close attention to during the treatment.

Anca negative pauci-immune crescentic glomerulonephritis and mixed connective tissue disease: a case study / Glomerulonefrite crescêntica pauci-imune ANCA-negativa e doença mista do tecido conjuntivo: relato de um caso

Abstract One of the most common causes of rapidly progressive glomerulonephritis (RPGN) is pauci-immune crescentic glomerulonephritis (CrGN). In the majority of cases, this condition has a positive serologic marker, the anti-neutrophil cytoplasmic antibodies (ANCAs), but in approximately 10% there are no circulating ANCAs, and this subgroup has been known as the ANCA-negative pauci-immune CrGN. RPGN can be associated with systemic diseases, but there are only few case reports describing the association with mixed connective tissue disease (MCTD). The authors report a case of ANCA-negative CrGN associated with a MCTD.

Resumo Uma das causas mais comuns da glomerulonefrite rapidamente progressiva (GNRP) é a glomerulonefrite crescêntica (GNC) pauci-imune. Na maioria dos casos, a patologia apresenta um marcador sorológico positivo, o anticorpo anticitoplasma de neutrófilos (ANCA), mas em cerca de 10% dos pacientes não há ANCAs circulantes, perfazendo um subgrupo da patologia conhecido como GNC pauci-imune ANCA-negativa. A GNRP pode estar associada a doenças sistêmicas, mas são poucos os relatos de caso que descrevem sua associação com doença mista do tecido conjuntivo (DMTC). O presente artigo relata um caso de GNC ANCA-negativa associada a DMTC.

Escleromixedema. Reporte de un caso / Scleromyxedema. Case report

Resumen Se presenta una paciente femenina con erupción papulosa generalizada que compromete cara, tronco y cuatro miembros. En el examen físico se visualizaengrosamientoy oscurecimiento de la piel. Se realiza el estudio integral y el correspondiente diagnóstico diferencial.El estudio histopatológico cutáneo exhibió un incremento excesivo de mucina intersticial, actividad fibroblástica y engrosamiento de los haces de colágeno. Se arriba al diagnóstico de escleromixedema debido a las manifestaciones cutáneas características. Se constata compromiso extracutáneo en ausencia de gammapatía monoclonal. Se indica prednisona, talidomida ehidroxicloroquina con excelente evolución.

Abstract A female patient presents with a generalized papular rash involving face, trunk, and four limbs. The skin is thickened and darkened, forming yellowish erythematous plaques that are linearly arranged papules. It is assumed as a generalized sclerodermiform syndrome and a comprehensive study and corresponding differential diagnosis is performed. The histopathological study of the skin showed an excessive increase of interstitial mucin, fibroblast activity and thickening of collagen bundles. The characteristic clinical expression and the histopathological study added to the extra cutaneous involvement lead to the diagnosis of scleromyxedema. There was no evidence of monoclonal gammopathy. Prednisone, thalidomide and hydroxychloroquine are indicated with excellent evolution.

The Prevalence Of Interstitial Lung Disease In Systemic Sclerosis Patients

OBJECTIVE: To report the prevalence of interstitial lung disease in Systemic Sclerosis patients at the Royal Hospital and compare our data with the literature. METHODS:All adult Omani patients with Systemic Sclerosis (SSc) who are under regular follow-up at the Royal Hospital were retrospectively enrolled from January 2006 to January 2014. RESULTS: A total of 49 cases of Systemic Sclerosis (SSc) patients were included. The mean age was 44.06 ± 11.9 years. There was a predominance of females (48 cases; 98%). Interstitial lung disease present in 30 cases (61%). The most frequent symptoms were dyspnea 47%, cough 33%, and others (e.g. atypical chest pain) 20%. There was no association with smoking, non-smoker (47 cases, 95.5%) versus ex. smoker (2 cases, 4%). The most high resolution computed tomography (HRCT) finding was traction bronchiectasis (21 cases, 42.9%) followed by honey comb appearance (19 cases, 38.8%). Pulmonary Function Test (PFT) was done in 33 cases. The mean total lung capacity (TLC) was 81. 06 ± 26.2. The mean diffusion lung capacity (DLCO) was 61.8± 28.3. Pulmonary hypertension was found in 10 cases only (20.4%) based on echocardiography. CONCLUSIONS: ILD was present in 30 cases out of 49 cases of SSc (61.2%) with female predominance. The most frequently observed HRCT change was traction bronchiectasis. Similarities and differences were found with respect to the previous reports from other countries.