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.

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 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.

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.

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.

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)

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.

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 5. Connective Tissue Disease Associated Interstitial Lung Disease / 결핵

Connective tissue disease (CTD) is a collection of disorders characterized by various signs and symptoms such as circulation of autoantibodies in the entire system causing damage to internal organs. Interstitial lung disease (ILD) which is associated with CTD is referred to as CTD-ILD. Patients diagnosed with ILD should be thoroughly examined for the co-occurrence of CTD, since the treatment procedures and prognosis of CTD-ILD are vary from those of idiopathic interstitial pneumonia. The representative types of CTD which may accompany ILD include rheumatoid arthritis, systemic sclerosis (SSc), Sjögren's syndrome, mixed CTD, idiopathic inflammatory myopathies, and systemic lupus erythematous. Of these, ILD most frequently co-exists with SSc. If an ILD is observed in the chest, high resolution computed tomography and specific diagnostic criteria for any type of CTD are met, then a diagnosis of CTD-ILD is made. It is challenging to conduct a properly designed randomized study on CTD-ILD, due to low incidence. Therefore, CTD-ILD treatment approach is yet to been established in absence of randomized controlled clinical trials, with the exception of SSc-ILD. When a patient is presented with acute CTD-ILD or if symptoms occur due to progression of the disease, steroid and immunosuppressive therapy are generally considered.

Clinical characteristics and treatment outcome of 147 cases of common connective tissue disease-related interstitial lung disease / 西安交通大学学报(医学版)

Objective: To investigate the clinical and imaging features of common connective tissue disease-related interstitial lung disease (CTD-ILD). Methods: We made a retrospective analysis of 147 cases of common CTD-ILD patients hospitalized in the Department of Rheumatology of The First Affiliated Hospital of Xi'an Jiaotong University from June 2014 to December 2016. Their clinical data including general information, manifestations, blood gas analysis, pulmonary function test, lung high resolution computed tomography (HRCT) were analyzed. Results: The average age of the 147 patients with common CTD-ILD was (56.2±12.3) years and the majority of the patients were women (72.1%). Skin lesions (51.7%) and fatigue (50.3%) were the most common clinical manifestations, which were higher than respiratory symptoms such as dyspnea (47.6%), expectotation (36.0%), and cough (32.0%). Nearly half (49.6%) of the patients had hypoxemia, and pulmonary function changes were mostly manifested as mixed ventilation dysfunction with diffuse dysfunction. Pulmonary imaging was characterized by ground-glass opacity (78.3%). The most common radiographic type was non-specific interstitial pneumonia (NSIP), accounting for 67.2%. During the follow-up period of 1-3.5 years, the mortality rate was 26.2%. PM/DM (66.7%) was higher than SSc (15.1%), RA (15.1%) and SS (3.0%). The main causes of death were infections (42.4%) and acute exacerbation of CTD-ILD (33.3%). Conclusion: The common CTD-ILD is predominant in women. The incidence of systemic symptoms such as skin changes and fatigue are higher than that of respiratory symptoms such as shortness of breath, cough and sputum. The mortality rate is high and the main causes are infections and acute exacerbation of CTD-ILD. Therefore, blood gas analysis, pulmonary function test and lung HRCT examination are helpful for diagnosis and treatment of CTD-ILD.

Pancreatitis y apendicitis aguda como complicación en una paciente con enfermedad mixta del tejido conectivo / Pancreatitis and acute appendicitis as a complication in a patient with mixed connective tissue disease

Introducción: la enfermedad mixta del tejido conectivo es una afección que incluye manifestaciones clínicas de diversas enfermedades reumáticas. Se caracteriza sobre todo por la presencia de afectación en todos los órganos y sistemas de órganos del cuerpo humano. Las complicaciones relacionadas con el aparato digestivo han sido señaladas como una de las que con mayor frecuencia se presentan. La pancreatitis y la apendicitis suelen presentarse de forma aislada, pero al presentarse al unísono complican más aún la evolución del paciente. Objetivo: dar a conocer los elementos clínicos, de laboratorio e imagenológicos que posibilitan llegar al diagnóstico de apendicitis y pancreatitis en una paciente con enfermedad mixta del tejido conectivo. Caso clínico: se presenta el caso de una paciente de 29 años de edad con diagnóstico de enfermedad mixta del tejido conectivo de 3 años de evolución que es remita al servicio de emergencia con elementos clínicos, de laboratorio e imagenológicos que permiten llegar al diagnóstico de una apendicitis y pancreatitis de presentación conjunta. Conclusiones: la enfermedad mixta del tejido conectivo es una enfermedad sistémica que cursa con una amplia variedad de manifestaciones clínicas y complicaciones. Los procesos agudos como la apendicitis y la pancreatitis suponen un peligro sobreañadido y un factor desencadenante de la actividad de la enfermedad(AU)

Introduction: mixed connective tissue disease is a condition that includes clinical manifestations of various rheumatic diseases. It is characterized above all by the presence of affectation in all organs and organ systems of the human body. Complications related to the digestive system have been identified as one of the most frequent. Pancreatitis and appendicitis usually occur in isolation, but when presented in unison, they complicate the evolution of the patient even more. Objective: to present the clinical, laboratory and imaging elements that make it possible to reach the diagnosis of appendicitis and pancreatitis in a patient with mixed connective tissue disease. Clinical case: the case of a 29-year-old patient with a diagnosis of mixed connective tissue disease of 3 years of evolution is presented, which is referred to the emergency service with clinical, laboratory and imaging elements that allow to reach the diagnosis of a appendicitis and pancreatitis of joint presentation. Conclusions: Mixed connective tissue disease is a systemic disease that presents with a wide variety of clinical manifestations and complications. Acute processes such as appendicitis and pancreatitis pose an added danger and a triggering factor in the activity of the disease(AU)

A evolução do diagnóstico da doença mista do tecido conjuntivo / Evolution of the diagnosis of mixed connective tissue disease

A Doença Mista do Tecido Conjuntivo (DMTC) é uma doença autoimune crônica composta por um misto de quatro doenças: Lúpus Eritematoso Sistêmico, Esclerose Sistêmica, Dermatomiosite/Polimiosite e Artrite Reumatoide. Por se tratar de uma combinação de doenças autoimunes o diagnóstico é bastante complexo. Atualmente existem quatro combinações sugeridas por diferentes autores para a realização de um diagnóstico preciso, são eles: Kasukawa, Alarcón-Segovia e Villareal, Kahn e Appeboom e Sharp. Desde a sua descoberta em 1972 por Sharp, passaram-se 46 anos e desta forma o objetivo desta revisão foi verificar a evolução do diagnóstico da DMTC desde a sua descoberta até a atualidade. Para isso utilizou-se sites de busca PUBMED e SCIELO. Por se tratar de uma doença autoimune que leva ao desenvolvimento de um quadro inflamatório crônico utilizou-se a ferramenta STRING que permite a análise da interação de proteínas. Até a presente data, não existe um consenso de qual critério deve ser usado para o diagnóstico correto e eficiente desta doença. A baixa relação de interações observadas a partir da ferramenta STRING demonstra que ainda não existem dados suficientes na literatura para que a ligação entre proteínas marcadoras e a DTMC possa ser estabelecida. (AU)

Mixed connective tissue disease (MCTD) is a chronic autoimmune disorder consisting of a mixture of four diseases: systemic lupus erythematosus, systemic sclerosis, dermatomyositis/polymyositis, and rheumatoid arthritis. Because it is a combination of different autoimmune disorders its diagnosis is quite complex. Currently there are four combinations suggested by the following authors to establish an accurate diagnosis: Kasukawa, Alarcón-Segovia & Villareal, Kahn, and Appeboom & Sharp. It has been 46 years since Sharp reported the disease in 1972 and thus the purpose of this review was to investigate the evolution of the diagnosis of MCTD since then. PubMed and SciELO databases were used for this investigation. Because MCTD is an autoimmune disease that leads to the development of a chronic inflammatory condition, the STRING tool was used to allow the analysis of protein interaction. To date, there is no consensus as to what criterion should be used for a correct and efficient diagnosis of this disease. The low ratio of interactions observed from the STRING tool demonstrates that there is not yet enough data in the literature for establishing the binding between marker proteins and MCTD. (AU)

Estudio multicéntrico descriptivo de enfermedades pulmonares intersticiales asociadas a enfermedades autoinmunes en centros de salud en Montevideo, Uruguay / Multicentric descriptive study of interstitial lung disease associated with autoimmune diseases in health centers in Montevideo, Uruguay / Estudio multicêntrico descritivo de enfermarias pulmonares intersticiales asociadas a enfermedades autoinmunes en centros de saúde en Montevideo, Uruguay

Resumen: Introducción: Las enfermedades pulmonares intersticiales (EPI) son una manifestación frecuente en algunas enfermedades autoinmune sistémica (EAIS). Objetivos: Describir las características de los pacientes que presentaron una EPI asociada a una EAIS, en centros de referencia de Montevideo. Valorar clínica, patrón imagenológico y severidad en pruebas de función respiratoria al momento diagnóstico. Metodología: Estudio multicéntrico descriptivo, observacional, de cohorte histórica, entre diciembre 2008 a diciembre 2017. Resultados: se enrolaron 59 pacientes, mujeres 88%, edad media 61 años. La clínica más frecuente fue la disnea. Las EAIS identificadas fueron: artritis reumatoidea (AR) 28%, esclerosis sistémica difusa (ESD) 22%, enfermedad mixta 6%, otras 42%. Debut con EPI previo a EAIS 9%; 47% presentó EPI en el primer año de diagnóstico de EAIS. Los patrones imagenológicos hallados fueron: neumonía intersticial no especifica (NINE) 64%, neumonía intersticial usual (NIU) 27%, neumonía organizativa 5%, neumonía intersticial linfoide 1%. Dentro del patrón NIU la enfermedad más prevalente fue la AR, en patrón NINE la ESD. La capacidad vital forzada (CVF) media fue de 80%, la DLCO media fue de 71%. En los pacientes con DLCO y CVF menor a 50% predominó la ESD. Conclusiones: la AR y ESD fueron las EAIS más asociadas a EPI. El diagnostico de EPI se realizó durante el primer año del diagnóstico de la EAIS, siendo NINE el patrón imagenológico más frecuente. El patrón NIU fue el más prevalente en AR y NINE en ESD.

Abstract: Introduction: The Interstitial Lung Disease (ILD) is a common manifestation from Connective Tisuue Disease (CTD). Objectives: Describe the characteristics of a population with ILD related to CTD in different hospitals of Montevideo. Analize the clinic manifestations, imagenologic pattern and severity of respiratory function evaluated by spirometry. Methods: Retrospective-descriptive of historical study of cohort, between 2008 december and december 2017. Results: 59 patients were enrolled, female 88%, mean age 61.The first symptom in diagnosis was dyspnea. The CTD identified were: Rheumatoid Arthritis (AR) 28%, Sclerodermia (SL) 22%, Mixed-CTD 7%. Debut of ILD before CTD 9%. The 47% of de patients have ILD in the first year of de diagnosis. The imagenologic pattern were: non specific interstitial pneumonia (NSIP) 65%, usual interstitial pneumonia (UIP) 27%, organizing pneumonia 5%, lymphocytic interstitial pneumonia (LIP) 1%. The most common illness in UIP pattern was AR, in NINE was SL. Forced vital capacity (FVC) media was 80%, DLCO media 71%, SL predominate in patients with FVC and DLCO less than 50%. Conclusions: AR and SL were the most common ILD. Almost half of the patients have ILD in the first year of the diagnosis, the NSIP pattern was the most frequent. UIP was most prevalent in AR and NSIP in SL.

Resumo: Introdução: A doença pulmonar infecciosa intersticial (EPI) tem uma manifestação frequente em várias doenças auto-imunes sistêmicas (EAIS). Objetivos: Descrever as características dos doentes que apresentam uma EPI associada a uma EAIS, nos centros de referência de Montevideu. Valorar clínica, patologia imaginária e gravidade em provas de função respiratória no momento diagnóstico. Metodología: Estudio multicêntrico descritivo, observacional, de cohorte, diciembre de 2008 a diciembre 2017. Resultados: se enrolaron 59 pacientes, mujeres 88%, edad media 61 godina. A clínica mais frecuente fue la disnea. Las EAIS têm fueron: artrite reumatóide (AR) 28%, esclerose sistêmica difusa (ESD) 22%, enfermedad mixta 6%, otras 42%. Estréia com EPI previo a EAIS 9%; 47% presentó EPI no primer año de diagnóstico de EAIS. Los patrones imagenológicos hallados fueron: neumonía intersticial não especifica (NOVE) 64%, neumonía intersticial usual (NIU) 27%, neumonía organizativa 5%, neumonía intersticial linfoide 1%. Dentro do parque NIU a enfermaria mais prevalente fue la AR, en patrón NINE la ESD. A capacidade vital forçada (CVF) media de 80%, o DLCO media de 71%. Os pacientes com DLCO e CVF menor a 50% predominaram na ESD. Conclusões: la AR e ESD fueron las EAIS más asociadas a EPI. O diagnóstico de EPI realiza-se durante o primer ano do diagnóstico do EAIS, siendo NINE o patrón imagenológico mais frecuente. El patrón NIU fue el mais prevalente en AR y NINE en ESD.

Pseudoxantoma elástico / Pseudoxanthoma elastic

Resumo O pseudoxantoma elástico é uma doença generalizada do tecido conjuntivo envolvendo a pele, olhos e sistema cardiovascular desencadeando a fragmentação e calcificação das fibras elásticas. Geralmente ocorre após a puberdade, as manifestações características são manchas pequenas, circunscritas, amareladas, localizadas no pescoço, axila e pregas inguinais. Estrias angioides na retina, tendência à hemorragia e insuficiência arterial são as complicações mais comuns. Esta doença pode ser herdada como autossômica dominante ou recessiva. O tratamento das manifestações oculares convencional é através da fototerapia a laser impedindo a ocorrência de hemorragias locais. Entretanto, novas abordagens terapêuticas estão sendo desenvolvidas como a utilização em longo prazo de drogas antiangiogênicas, as quais atuam inibindo a neovascularização ocular. Apesar de não ter ainda efetivamente substituído o tratamento original, pesquisas recentes já evidenciam benefícios da nova técnica. O objetivo deste estudo é relatar sobre o caso de uma paciente de 37 anos, portadora do pseudoxantoma elástico, com estrias angioides e hemorragia ocular, e o tratamento eficaz com a terapia antiangiogênica no ambulatório de oftalmologia em Nova Iguaçu, Rio de Janeiro.

Abstract The pseudoxanthoma elasticum is a generalized disease of the connective tissue involving the skin, eyes and cardiovascular system triggering the fragmentation and calcification of elastic fibers. Usually occurs after puberty, the manifestations characteristics are small spots, circumscribed, yellowish, located on the neck, axilla and inguinal folds. Angioid streaks in the retina, tendency to hemorrhage and arterial insufficiency are the most common complications. This disease can be inherited as autosomal dominant or recessive. The treatment of ocular manifestations is through the conventional phototherapy laser preventing the occurrence of local hemorrhages. However, new therapeutic approaches are being developed as the long-term use of drugs antiangiogenic, which act by inhibiting the ocular neovascularization. Despite not having yet effectively replaced the original treatment, recent research already show benefits of new technique. The objective of this study is to report on a case of a patient of 37 years, the carrier of the Pseudoxanthoma Elasticum, with angioid streaks and ocular hemorrhage, and the effective treatment with antiangiogenic therapy at the clinic of Ophthalmology in Nova Iguaçu, Rio de Janeiro.

2018 Chinese expert-based consensus statement regarding the diagnosis and treatment of interstitial lung disease associated with connective tissue diseases / 中华内科杂志

To establish the experts consensus on diagnosis and treatment of interstitial lung disease (ILD) associated with connective tissue diseases (CTDs). A multidisciplinary consensus development panel was established. The panel of consensus was composed of 41 experts in rheumatology, pulmonology, radiology, most of whom were members of Group of Pulmonary Vascular and Interstitial Diseases Associated with Rheumatic Diseases. The consensus development panel developed 3 major principles and 7 recommendations for the diagnosis and treatment of ILD associated with CTDs. The consensus covered the early screening, diagnosing, disease monitoring and assessing, immunosuppressive and anti-fibrotic therapy with a treat-to-target approach. This consensus was intended to facilitate the decision-making and standardize the care of ILD associated with CTDs in China.

Pulmonary Hypertension in Connective Tissue Disease is Associated with the New York Heart Association Functional Class and Forced Vital Capacity, But Not with Interstitial Lung Disease

OBJECTIVE: Pulmonary hypertension (PH) develops frequently in connective tissue diseases (CTD) and is an important prognostic factor. The aim of this study was to assess the prevalence of PH in patients with CTD by non-invasive echocardiography and analyze the potential biomarkers for helping to detect PH. METHODS: All Korean patients with CTD who had dyspnea on exertion or interstitial lung disease (ILD) were screened for PH with echocardiography and clinical data were collected from four hospitals. RESULTS: Among 196 patients with CTD, 108 (55.1%) had ILD and 21 had PH defined as >40 mmHg. Of the 21 patients with PH, 10, 4, and 3 patients had systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease, respectively. There was no difference in the incidence of PH according to the presence of ILD; 12 patients (11.1%) with ILD had PH and 9 patients (10.2%) without ILD had PH. The results of the pulmonary function test, total cholesterol, red cell volume distribution width, alkaline phosphatase, and the New York Heart Association (NYHA) functional class III or IV differed significantly according to the presence of PH. In multiple regression analysis, NYHA functional class III or IV (odd ratio [OR]=7.3, p=0.009) and forced vital capacity (OR=0.97, p=0.043) were independent predictive factors of PH. CONCLUSION: PH is not associated with the presence of ILD in Korean patients with CTD. On the other hand, NYHA functional class III or IV and decreased forced vital capacity indicate the presence of PH in connective tissue disease.

Comparative study of clinical and HRCT findings between idiopathic nonspecific interstitial pneumonia and connective tissue disease-associated nonspecific interstitial pneumonia / 实用医学杂志

Objective To investigate the difference in clinical features and chest HRCT findings between idiopathic nonspecific interstitial pneumonia(INSIP)and connective tissue disease-associated nonspecific interstitial pneumonia(CTD-NISP). Methods Totally 73 cases of NISP from 2011 to 2016 were retrospectively reviewed ,whose final diagnosis all were made after clinico-radiologic-pathologic discussion and 52 cases of them were diag-nosed as INSIP and 21 cases as CTD-NSIP. Clinical features ,lung function test results and chest HRCT findings of INSIP and CTD-NSIP were compared. Results Common underlying diseases of CTD-NSIP were poly-/dermato-myositis(PM/DM),rheumatoid arthritis(RA)and Sjogren syndrome(SS). The mean age of CTD-NSIP[(47.14 ± 9.24)y]was younger than that of INSIP[(59.09 ± 11.20)y](P<0.05). Compared to CTD-NSIP,expectoration was more common in patients with INSIP,while dry mouth/eyes,arthralgia and erythra were less common in INSIP (P < 0.05). Lung function test1 showed restrictive ventilatory dysfunction with dispersion function decline was found in both groups. There were no significant differences in lung function test results between INSIP and CTD-NSIP. In HRCT,the subpleural vertical line was more common in INSIP than that in CTD-NSIP,while patchy consolidation,subpleural curvilinear shadow,pleural effusion and esophageal dilation were less common in INSIP(P<0.05). Conclusions Specific difference of clinical and HRCT features between CTD-NSIP and INSIP are conducive to differentiating the two from each other.

Neutrophil extracellular traps-induced endothelial cell damage in the pathogenesis of dermatomyositis-associated interstitial lung disease / 中华内科杂志

Objective To explore the role of neutrophil extracellular traps (NETs)-induced endothelial cell damage in the pathogenesis of dermatomyositis (DM)-associated interstitial lung disease (ILD).Methods Serum free DNA and krebs von den lungen-6 (KL-6) level were tested in healthy controls,dermatomyositis patients with or without interstitial lung disease (DM-ILD and DM-NILD).Subjects' peripheral blood neutrophils were stimulated with phorbol 12-myristate 13-acetate (PMA),then human umbilical vein endothelial cells (HUVECs) were co-cultured with NETs.The cell morphology was observed by the inverted phase contrast microscope.Cell viability was detected by cell counting kit-8 (CCK8).Results The concentration of serum free DNA in DM patients [(271.27 ± 76.53) μg/L] was significantly higher than that in health control (HC) [(152.89 ± 37.34) μg/L,P ＜ 0.001].Moreover,free DNA level in DM-ILD patients [(302.67 ± 74.15) μg/L] was higher than that in DM-NILD patients [(235.59 ±63.55) μg/L,P ＜0.005].The concentration of KL-6in DM patients [(3.08 ±2.07) μg/L] was higher than that in HC [(0.87 ± 0.51) μg/L,P ＜ 0.001].Similarly,KL-6 in DM-ILD patients [(4.00 ± 2.44) μg/L] was higher than that of DM-NILD patients [(2.03 ± 0.61) μg/L,P ＜ 0.005].Free DNA and KL-6 were positively correlated (r =0.251,P ＜ 0.05).The survival of endothelial cells in DM group (53 ± 11) ％ was lower than that of HC group [(70 ± 5) ％,P ＜ 0.001].Not surprisingly,the survival of endothelial cells in DM-ILD group (44 ±4) ％ was lower than that in DM-NILD group [(61 ± 8) ％,P ＜ 0.01].Conclusion NETs could play an important role in the pathogenesis of dermatomyositis associated interstitial lung disease,suggesting that NETs may be the potential therapeutic target.