Relación entre los anticuerpos contra antígenos extraíbles del núcleo y las enfermedades del tejido conectivo identificados por Immunoblots en un hospital y universidad de Lima / Relationship between antibodies against extractable nucleus antigens and connective tissue diseases identified by Immunoblot in a hospital in Lima, Peru

Objetivos: Determinar la relación de los anticuerpos con los antígenos del núcleo extraíble y las enfermedades del tejido conectivo identificadas por Immunoblot en un hospital de Lima, Perú. Material y métodos: Estudio de tipo observacional, ciencias básicas, analíticas y transversales, realizado en el Servicio de Inmunología del Hospital Nacional Arzobispo Loayza entre enero de 2018 y junio de 2018. Analizamos 291 historias clínicas de pacientes con enfermedad del tejido conectivo y para la detección de anticuerpos contra los antígenos extraíbles del núcleo se empleó el método de Immunoblots. Resultados: La frecuencia de los anticuerpos contra antígenos nucleares extraíbles en pacientes con enfermedad del tejido conectivo identificados por Immunoblot fue 789 (100%). Se demostró que existe una relación significativa p <0.05 de Anti-histonas (X2 = 64.19; p = 0,000), anti-nucleosomas (X2 = 71,16; p = 0,000), anti-dsDNA (X2 = 71,44; p = 0,000), anti-SM (X2 = 10,08; p = 0,003) y lupus eritematoso sistémico con prueba de Chi-cuadrado de Pearson. Se demostró que existe una relación significativa p <0.05 del Anti-SSA (X2 = 61,33; p = 0.001), anti-SSB (x2 = 51,00; p = 0.001), anti-Ro 52 (X2 = 62,60; p = 0,000) y síndrome de Sjogren con prueba de Chi-cuadrado de Pearson. Se demostró que existe una relación significativa p <0.05 de Anti-CENP B (p = 0.001) y calcinosis, fenómeno de Raynaud, dismotilidad esofágica, esclerodactilia y Telangiectasia (CREST) con Fisher. Conclusiones: Existe relación de anticuerpos con antígenos de núcleo extraíbles y lupus eritematoso sistémico, síndrome de Sjogren, enfermedad mixta del tejido conectivo, enfermedad del CREST, esclerodermia y polimiositis.

Objectives: To determine the relationship of antibodies to extractable nucleus antigens and connective tissue diseases identified by Immunoblot in a hospital in Lima, Peru. Material and methods: Study of the observational type, basic sciences, analytical and transversal, carried out in the Immunology service of the national Hospital Archbishop Loayza between January 2018 and June 2018. We analyzed 291 clinical histories of patients with connective tissue disease and for the detection of antibodies to the extractable antigens of the nucleus the method of Immunoblot was employed. Results: The frequency of the antibodies against extractable nuclear antigens in patients with connective tissue disease identified by Immunoblot was 789 (100%). It was demonstrated that there is significant relationship p < 0.05 of Anti-histones (X2 = 64.19; p = 0,000), anti-nucleosomas (X2 = 71,16; p = 0,000), anti-dsDNA (X2 = 71,44; p = 0,000), anti-SM (X2 = 10,08; p = 0,003) and Lupus Systemic erythematosus with Pearson Chi-square test. It was demonstrated that there is significant relationship p < 0.05 of the Anti-SSA (X2 = 61,33; p = 0.001), anti-SSB (X2 = 51,00; p = 0.001), anti-Ro 52 (X2 = 62,60; p = 0,000) and Sjogren's syndrome with Pearson Chi-square test. It was demonstrated that there is significant relationship p < 0.05 of Anti-CENP B (p = 0.001) and calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and Telangiectasia (CREST) with exact Fisher statistician. Conclusions: There is a relationship of antibodies to extractable nucleus antigens and systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and Telangiectasias (CREST), Scleroderma and Polymyositis.

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.

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)

Indicação de oxigenioterapia hiperbárica como auxiliar na cicatrização de úlceras de membro inferiores / Indication of hyperbaric oxygen therapy as an aid in healing lower limb wounds

Esse artigo refere-se a um caso de perícia médica solicitada por motivo de ação judicial movida por paciente do sexo masculino de 49 anos de idade contra o município de Ipatinga, MG. O periciando é sabidamente portador de Doença Mista do Tecido Conjuntivo e Síndrome de Anticorpo Antifosfolípide, tendo desenvolvido, como consequência dessa última patologia, úlcera venosa crônica em membro inferior, não cicatrizada mesmo após duas cirurgias de enxertia. O paciente requer perante o juízo, por indicação de sua médica reumatologista, que o município arque com o procedimento de oxigenioterapia hiperbárica, considerando-se sua eficácia potencial na cicatrização de feridas. Deixando as considerações jurídicas do caso à parte, como médica perita do banco de peritos do Tribunal de Justiça de Minas Gerais, depois de avaliar clinicamente o paciente, realizei revisão da literatura médicocientífica no que diz respeito aos benefícios e indicações dessa forma de terapia para o mesmo. O objetivo desse artigo é descrever acerca desse procedimento médico, bem como esclarecer suas indicações e limitações, especialmente no que tange ao caso concreto apresentado. (AU)

This paper refers to a medical inquiry related to a lawsuit against Ipatinga County (MG), in which a male patient aged 49 years old requests the right to receive 60 sessions of hyberbaric oxygen therapy (HBOT), as an aid to healing wounds. The patient has been previously diagnosed with Mixed Disease of the Connective Tissue and Antiphospholipid Syndrome, having developed, as result of the latter disease, a chronic venous ulcer in the lower limb, not healed even after two grafting surgeries. Towards the Court, the patient requires the delivery of HBOT, considering its potential effectiveness in wound healing. Leaving apart the legal considerations of the case, as a medical expert of the Justice Court of Minas Gerais (TJMG), after a detailed clinical evaluation of the patient, I reviewed the medical literature regarding the benefits and indications of this form of therapy, correlating them to this concrete case. The aim of this article is to describe this relatively new medical procedure, and to clarify its indications and limitations, particularly with regard to the present case. (AU)

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.

Co-existent Mixed Connective Tissue Disease and Papillary Thyroid Cancer in a Patient with Primary Biliary Cirrhosis / 대한내과학회지

A 40-year-old female previously diagnosed with primary biliary cirrhosis was referred to the hospital complaining of muscle weakness, arthralgia, Raynaud's phenomenon, and thick skin. After work-up, she was diagnosed with both mixed connective tissue disease (MCTD) and papillary thyroid cancer (PTC), based on the Alarcon-Segovia criteria and pathological examination, respectively. High-dose glucocorticoid and azathioprine were introduced to treat active myositis of MCTD, and total thyroidectomy was performed to treat PTC. This report highlights the possible association between MCTD and thyroid cancer, and suggests that MCTD is associated with PTC, similar to other autoimmune diseases including Sjögren's syndrome, systemic sclerosis, and systemic lupus erythematosus.

Aplicación de un algoritmo para la detección de hipertensión arterial pulmonar en pacientes con enfermedad del tejido conectivo / Application of an Algorithm for the Detection of Pulmonary Arterial Hyertension in Patients with Connective Tissue Disease

Introducción: La hipertensión pulmonar (HP) es una complicación grave que se puede presentar en las enfermedades del tejido conectivo (ETC), múltiples causas pueden ser el origen de la misma. Por lo tanto, es imprescindible establecer un diagnóstico preciso para determinar la causa de la HP. Los algoritmos de diagnóstico precoz están dirigidos a la detección temprana de la HP en pacientes con ETC Objetivos: 1) detectar la presencia de HP en una población con diagnóstico de ETC mediante un algoritmo de detección precoz y 2) diagnosticar HAP asociada a ETC. Materiales y Métodos: Estudio descriptivo, prospectivo. Se incluyeron pacientes adultos en control y seguimiento reumatológico, con diagnóstico de ETC sintomática o esclerosis sistémica/enfermedad mixta del tejido conectivo (EMTC) sintomática como asintomática. A aquellos pacientes con alta sospecha clínico-ecocardiográfica de HP se les realizó cateterismo cardíaco derecho (CCD). Resultados: Se incluyeron 90 pacientes, 82 mujeres (91%) y 8 hombres (9%), con una edad media de 52 años. Presentaban esclerosis sistémica 54 (60%), artritis reumatoidea 18 (20%), EMTC 8 (9%), lupus eritematoso sistémico 8 (9%), Sjögren 1 (1%), polimiositis 1 (1%). La presencia de disnea fue referida en 60 pacientes (67%); un total de 12 pacientes (13%) presentaron alta presunción de HP y se les realizó un CCD, confirmándose el diagnóstico de HP en 9 (10%), siendo 7 del grupo I HAP y 2 del grupo II. Los pacientes con HP del grupo I se encontraban distribuidos según Clase funcional (CF), de la siguiente manera: uno en CF III, cinco en CF II y uno en CF I. Conclusiones: EI algoritmo utilizado permite diagnosticar HAP en pacientes con ETC en etapas termpranas.

Introduction: Pulmonary hypertension (PH) is a serious complication in connective tissue disease (CTD), although multiple causes can be the source of it. Therefore, it is essential to establish an accurate diagnosis to determine the cause of HP. Early detection algorithms are aimed to diagnose PH in patients with CTD in less advanced disease. Objectives: 1) To detect the presence of pulmonary hypertension (PH) in a population diagnosed with CTD by an early detection algorithm. 2) To diagnose Pulmonary arterial hypertension (PAH) associated to CTD. Materials and Methods: It's a descriptive, prospective study. Adult patients diagnosed with symptomatic CTD or symptomatic and asymptomatic systemic sclerosis, mixed connective tissue disease (MCTD) in the setting of rheumatologic control were included. Those patients with high clinical and echocardiographic suspicion of PH were catheterized (CCD). Results: 90 patients, 82 women (91%) were included, with a median age of 52 years. Fifty-flour (60%) corresponding to Systemic sclerosis, 18 (20%) to rheumatoid arthritis, 8 (9%) to MCTD, 8 (9%) to systemic lupus erythematosus, 1 (1%) to Sjögren and 1(1%) to polymyositis. Dyspnea was referred in 50 patients (67%); 12 patients (13%) had high presumption of HP and underwent a CCD, confirming the diagnosis of HP in 9 (10%). Sever belonged to PH Group I and 2 to group II. PH group I patients were distributed according to functional class (FC), as follows: 1 FC III, 5 FC II and 1 FC I. Conclusions: The used algorithm allows early PAH diagnosis in CTD.

The Clinical Efficacy of Nailfold Capillaroscopy in Rheumatic Diseases / 대한내과학회지

Nailfold capillaroscopy (NFC) is a non-invasive morphological study that routinely used to differentiate between a primary and secondary Raynaud's phenomenon (RP). Secondary RP is a manifestation of an underlying rheumatic disease that occurs in 80-95% of patients with systemic sclerosis (SSc), 75% of patients with mixed connective tissue disease and in 20-25% of patients with systemic lupus erythematosus or rheumatoid arthritis. These RP frequently precedes the underlying disease by many years. The well-established roles of NFC are the early diagnosis of SSc, and potential for predicting clinical complication, as like digital ulcers. The following review will present a technique about how to perform NFC and optimal assessment with emphasis on its possible role as a reliable diagnostic tool.

Manejo de las enfermedades intersticiales en Argentina: Una encuesta a neumonólogos / Management of Interstitial Lung Diseases in Argentina: a Survey to Pulmonologists

Introducción: Las enfermedades pulmonares intersticiales difusas (EPID) son un grupo de enfermedades raras que, si bien comparten ciertas características clínicas, tienen un pronóstico muy diferente. La fibrosis pulmonar idiopática (FPI) es la más prevalente en muchos países y su diagnóstico puede ser dificultoso. Luego de los resultados expuestos en el consenso sobre diagnóstico y manejo de la FPI, y la llegada de nuevas drogas como la pirfenidona, se ha modifcado el enfoque de esta enfermedad. Se realizó una encuesta a neumonólogos argentinos, con el fin de evaluar la aceptabilidad e implementación de estas guías en Argentina. Materiales y métodos: Se diseñó una encuesta con 24 preguntas. Entre los datos que se recolectaron en el cuestionario estaban demografía de los encuestados, lugar de trabajo (instituciones públicas, privadas, grandes o pequeños centros o instituciones), frecuencia con la que evaluaban pacientes con FPI, disponibilidad de pruebas diagnósticas y estrategias diagnósticas empleadas para pacientes con EPID. Por último, la encuesta se focalizó en las recomendaciones terapéuticas en los pacientes diagnosticados como FPI. Dicha encuesta fue completada durante el Congreso Argentino de Medicina Respiratoria que se realizó en el 2013 en la ciudad de Mendoza. La misma metodología y cuestionario fueron utilizados previamente en el Congreso Argentino de Medicina Respiratoria del 2011. Resultados: Un total de 252 médicos respondieron la encuesta en el 2013, lo que representó alrededor del 20% de los concurrentes al congreso. El método complementario de mayor disponibilidad fue la prueba de marcha de 6 minutos (PM6M). El método complementario más utilizado fue la tomografía computada de tórax (86.9% de los encuestados la realizaban ante la sospecha de EPID) y solo el 44.4% de los encuestados realizaban difusión de monóxido de carbono (DLCO) en todos sus pacientes. Cerca del 50% de los encuestados consultaban a centros de referencia en menos del 30% de sus casos con sospecha de EPID. Menos del 20% de los respondedores consideraban que llegaban a un diagnóstico defnitivo de EPID en más del 60% de sus pacientes. La distribución final de los diagnósticos fue heterogénea. Notablemente, casi el 50% de los encuestados consideraba que la FPI había sido el diagnóstico final en menos de 30% de sus pacientes. Solo el 30% de los encuestados prescribieron pirfenidona como tratamiento de elección en la FPI y más del 60% todavía continuaban prescribiendo tratamientos que incluían diferentes combinaciones de corticoides e inmunosupresores. Conclusiones: Nuestra encuesta sugiere que existen dificultades en el abordaje diagnóstico de estas entidades, que existe un bajo porcentaje de pacientes que son evaluados en centros de referencia y que hay una baja proporción de estos que reciben tratamiento específico.

Background: Diffuse interstitial (or parenchymal) lung diseases (ILDs) are a very large group of diseases that although they share certain clinical features, have a very different prognosis. Idiopathic pulmonary fibrosis (IPF) is the most prevalent in many countries and its diagnosis can be difficult. After the results shown in the consensus on diagnosis and management of IPF, and the arrival of new drugs such as pirfenidone, the approach to this disease have changed. A survey was performed to argentine pulmonologists in order to evaluate the acceptability and implementation of these guidelines in Argentina. Material and Methods: A survey of 24 questions was designed. Among the data collected in the questionnaire were demographics of respondents, workplace (public or private healthcare facilities, referral center, large or small healthcare centers or institutions), frequency at which IPF patients were examined, availability of diagnostic tests, and diagnostic strategies used with ILD patients. Finally, the survey focused on therapeutic recommendations for patients diagnosed with IPF. The survey was completed during the Argentine Congress of Respiratory Medicine held in 2013 in the city of Mendoza. The same methodology and questionnaire were previously used in the Argentine Congress of Respiratory Medicine in 2011. Results: In 2013, a total of 252 physicians completed the survey, which represented approximately 20% of Congress attendees. The complementary test of higher availability was the the six minutes walk test (6MWT). The most widely used supplementary method was thoracic computed tomography (CT) as 86.9% of the responders used it if they suspected ILD, and only 44.4% of the responders used diffusing capacity of the lungs for carbon monoxide (DLCO) with all their patients. Almost 50% of the responders consulted referral centers for less than 30% of patients with suspected ILD. Less than 20% of the responders considered that they reached a final diagnosis of ILD in over 60% of their patients. Final distribution of diagnosis was heterogeneous. Interestingly, almost 50% of the responders considered IPF as the fnal diagnosis in less than 30% of their patients. Approximately 50% of the responders answered that less than 20% of their IPF patients received specifc treatment for the disease. Conclusions: Our survey suggests that there are difficulties in the diagnostic approach of ILDs, there is a low percentage of patients that are evaluated in referral centers and there is a low proportion of IPF patients receiving specific treatment

Supervivencia en pacientes con neumonía intersticial usual en contexto de fibrosis pulmonar idiopática y enfermedad del tejido conectivo / Survival in Patients with Usual Interstitial Pneumonia Secondary to Idiopathic Pulmonary Fibrosis and Connective Tissue Disease

Introducción: La neumonía intersticial usual (NIU) es un patrón histológico que conlleva mal pronóstico. Sin embargo, en los últimos años se ha sugerido que la NIU asociada a las enfermedades del tejido conectivo (NIU-ETC) puede tener un comportamiento diferente a la asociada a la fibrosis pulmonar idiopática (FPI). Objetivos: Conocer si existen diferencias en la severidad y supervivencia entre los pacientes con NIU asociada a FPI y los pacientes con NIU en contexto de ETC, incluyendo esclerosis sistémica, artritis reumatoidea, polidermatomiositis y enfermedad mixta del tejido conectivo. Materiales y métodos: Fueron evaluadas las características clínicas y la supervivencia de 102 pacientes (81 con FPI y 21 con NIU-ETC) diagnosticados en base a biopsia quirúrgica o una tomografía computada de alta resolución (TCAR) con NIU definida. Resultados: La media de seguimiento fue de 24 meses (0 a 146 meses). Cuarenta y cuatro pacientes murieron durante el seguimiento, una proporción significativamente mayor entre los pacientes con FPI que entre los pacientes con NIU-ETC (49.4 vs 19.0%, p = 0.014) y la supervivencia a 3 y 5 años fue mayor en pacientes con NIU asociada a ETC que en pacientes con FPI. Los pacientes con NIU-ETC tuvieron una tasa de mortalidad a los 3 y 5 años de 19.5% y 20.0%, respectivamente, comparado con pacientes con FPI que tuvieron una tasa de mortalidad a 3 y 5 años de 35.0%, y 65.9% respectivamente (p = 0,014). Los pacientes con FPI fueron mayores que los pacientes con NIU-ETC (edad 67.95 ± 9.4 vs 57.78 ± 14.5, p = 0.021), con una proporción mayor de pacientes de sexo masculino (67.9% vs 33.3%, p = 0.006). No hubo diferencias significativas en la función pulmonar basal, la cantidad de pacientes con disnea en el momento del diagnóstico, el tiempo de inicio de síntomas al diagnóstico o en número de pacientes biopsiados entre ambos grupos. En el análisis multivariado, la DLCO y el diagnóstico de FPI fueron los únicos factores pronósticos independientes. Conclusiones: Nuestro estudio sugiere que los pacientes con NIU-ETC se asocian con una mejor supervivencia que aquellos pacientes con FPI, a pesar de presentar la misma severidad de enfermedad al momento del diagnóstico.

Background: Usual interstitial pneumonia (UIP) is a histologic pattern that implies poor prognosis. However, some studies have suggested that UIP associated to connective tissue diseases (CTD-UIP) may have a different outcome than that associated with idiopathic pulmonary fibrosis (IPF). Objectives: To compare disease severity and survival between IPF and UIP associated to connective tissue diseases including scleroderma, rheumatoid arthritis, polymyositis and mixed CTD. Methods: The study included the analysis of clinical features and survival of 102 patients (81 with IPF and 21with CTD-UIP) diagnosed through surgical biopsy or high resolution computed tomography (HRCT) in patients with definitive UIP. Results: Median follow-up was 24 months (0 to 146 months). Forty-four patients died during the follow-up; the proportion of deaths was significantly higher amongst patients with IPF than amongst patients with CTD-UIP (49.4 vs 19.0%, p = 0.014). The 3 and 5 year survival was higher in patients with UIP secondary to CTD than in patients with IPF. Patients with CTD-UIP showed 3 and 5-year case fatality rate of 19.5% and 20.0% respectively, compared to 3 and 5-year case fatality rate of 35.0%, and 65.9% respectively in patients with IPF (p = 0.014). Patients with IPF were older than patients with CTD-UIP (age 67.95 ±9.4 vs 57.78 ±14.5, p = 0.021) and were more likely to be male (67.9% vs 33.3%, p = 0.006). There were no significant differences among baseline lung function, time between onset of symptoms and diagnosis, number of patients biopsied and the proportion of patients with dyspnea at the time of diagnosis between IPF and CTD-UIP patients. By multivariate analysis, the diffusing capacity of the lung for carbon monoxide (DLCO) and the presence of IPF were independent prognostic factors. Conclusions: Our data suggest that patients with UIP associated to CTD have a better survival than patients with IPF related UIP despite similar disease severity at the time of the diagnosis.

Mycobacterium chelonae cutaneous infection in a patient with mixed connective tissue disease

Around 50 mycobacteria species cause human disease. Immunosuppressive states predispose to non-tuberculous mycobaterium infection, such as Mycobacterium chelonae: AFB, non-tuberculous, fast growth of low virulence and uncommon as a human pathogen. It may compromise the skin and soft tissues, lungs, lymph nodes and there is also a disseminated presentation. The diagnosis involves AFB identification and culture on Agar and Lowenstein-Jensen medium base. A 41-year-old female with MCTD (LES predominance) is reported, presenting painless nodules in the right forearm. She denied local trauma. Immunosuppressed with prednisone and cyclophosphamide for 24 months. Lesion biopsy has demonstrated positive bacilloscopy (Ziehl-Neelsen stain) and M.chelonae in culture (Lowenstein-Jensen medium base), therefore clarithromycin treatment has been started (best therapy choice in the literature).

A Case of Bad Prognosis for Membranous Nephropathy in a Patient with Mixed Connective Tissue Disease

Incidence of renal involvement in mixed connective tissue disease (MCTD) is low. In the presence of glomerulonephritis, membranous nephropathy (MN) in MCTD is common. A 47-year-old woman presented with hypothyroidism. She developed Raynaud's phenomenon, arthralgia, and incomplete lupus erythematosus, diagnosed with MCTD. One year after then, the patient developed persistent proteinuria (1+) without hematuria. Following diagnosis with MCTD, her renal function began to deteriorate. The renal biopsy showed late stage MN. For the treatment of MN with mild proteinuria and MCTD, we prescribed an angiotensin II receptor blocker and 7.5 mg of methotrexate per week and 300 mg of hydroxychloroquine daily. The patient had a reduced estimated glomerular filtration rate of 55% for the subsequent eight years. The MN in MCTD is known to show good renal prognosis. Here, we report on a rare case of MN in MCTD in Korea with a bad prognosis.

Sjogren's syndrome: An underdiagnosed condition in mixed connective tissue disease

OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögren's syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawa's criteria) and 41 healthy controls underwent Schirmer's test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögren's syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years) and frequencies of female gender (93 vs. 95%) and Caucasian ethnicity (71.4 vs. 85%). Ocular symptoms (47.7 vs. 24.4%) and oral symptoms (52.3 vs. 9.7%) were significantly more frequent in patients than in controls. Fourteen (31.8%) patients fulfilled Sjögren's syndrome criteria, seven of whom (50%) did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögren's syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögren's syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögren's syndrome (92.8%). CONCLUSIONS: Sjögren's syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients. .

Mixed connective tissue disease in Filipinos - A 13-year retrospective review of 14 cases in the Philippine General Hospital

BACKGROUND: Mixed connective tissue disease (MCTD) is a distinct autoimmune disease with overlapping features of different connective tissue diseases and a broad spectrum of presentation and prognosis. Our aim is to present the clinical profile of a cohort of Filipinos with MCTD.METHODS: Charts with diagnosis of MCTD based on the Alarcon-Segovia Criteria from the Philippine General Hospital Adult Rheumatology clinic from January 1999 to December 2011 were reviewed for demographics, clinical presentation, and management. Descriptive statistics were applied.RESULTS: Fourteen patients were identified to have MCTD. All were females. The median age at symptom onset, and at diagnosis, was 30.5, and 31.5 years, respectively, with two having juvenile onset of symptoms. Mean interval from symptom onset to diagnosis is two years. Patients are being followed up for the past mean of 3.5 years.All eight women    who wanted children were able to conceive, and among them only two had fetal losses but were negative for antiphospholipid antibodies. Chief complaint was most commonly joint pain (67%) followed by skin tightness (13%). Systemic lupus erythematosus (SLE) was the most frequent initial diagnosis (43%). Majority had initial constitutional symptoms with generalized weakness and fatigue being the most frequent (93%). Most common physical findings in different body systems are as follows: musculoskeletal - arthritis (100%); vascular - Raynaud's phenomenon (93%); cutaneous- skin tightness (71%); gastrointestinal - dental caries (57%); hematologic - anemia of chronic disease (50%); cardiopulmonary - accentuated pulmonary component of the second heart sound and right ventricular hypertrophy (21% each); neurologic - peripheral neuropathy (21%); renal - proteinuria (21%); endocrine - autoimmune thyroiditis (21%).Half have anemia of chronic disease. Only three (21%) have proteinuria and were below nephrotic range. Twelve out of 12 have elevated sedimentation rates. For serologic studies, all have speckled ANA  and very  high  titers  of  anti-U1RNP;six of six patients have  normal  rheumatoid  factor(RF) titers; one    out    of  two  have  positive  anti-Ro;two out of four have anti-Ds DNA; none of two have anti-SCL70.Majority of the chest x-rays,electrocardiograms,echocardiographs  were  normal.Three have pulmonary hypertension. One out of four has restrictive lung disease on pulmonary function test. Most are in remission and are on low-dose prednisone (79%), hydroxychloroquine (50%), nifedipine (36%) and methotrexate (21%).CONCLUSION: This is the first study that detailed clinical and laboratory features of Filipinos with MCTD diagnosed using the Alarcon-Segovia criteria. Most clinical features, disease activity, and management are concordant with international data. Possible peculiarities include fewer interstitial lung disease, esophageal dysmotility, thrombocytopenia and leucopenia, and RF titers. We intend to add newly diagnosed patients and pursue this cohort for us to better understand the course of MCTD in Filipinos that could translate to better patient care.

ANCA associated glomerulonephritis in a patient with mixed connective tissue disease / 中南大学学报(医学版)

OBJECTIVE@#To investigate the diagnosis and treatment of mixed connective tissue disease (MCTD) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis, which is a rare clinical entity in medical practice.@*METHODS@#A 35-year-old female of Asian origin was admitted to our hospital due to complaints of Raynaud's phenomenon, myalgia, arthralgia and fatigue. The patient was diagnosed as MCTD in the out-patient department 8 months prior to admission based on Alarcon-Segovia classification criteria of Raynaud's phenomenon, myalgia, arthralgia and a high anti-U1 ribonucleoprotein antibody level. Interstitial lung disease was determined by chest computed tomography. Renal biopsy was performed because of marked proteinuria on 24 h urine collection. Histopathological examination revealed glomerulonephritis with fibrocellular/cellular crescents, in which moderate staining of IgM was shown by direct immunofluorescence. She was tested positive for myeloperoxidase antineutrophil cytoplasmic antibody.@*RESULTS@#High dose of methylprednisolone (500 mg/d for 3 days) was started intravenously when the results of renal biopsy were obtained. Oral prednisone and intravenous cyclophosphamide therapy (0.8 g/month) were continued for 12 months. Daily urinary protein loss decreased dramatically and serum creatinine was maintained at a normal level.@*CONCLUSION@#Corticosteroids and cyclophosphamide are effective in the treatment of MPO-ANCA associated glomerulonephritis in MCTD.

Cutaneous mucinosis in mixed connective tissue disease* / Mucinose cutanea na doenca mista do tecido conjuntivo

Cutaneous mucinosis is a group of conditions involving an accumulation of mucin or glycosaminoglycan in the skin and its annexes. It is described in some connective tissue diseases but never in association with mixed connective tissue disease. This report concerns two cases of cutaneous mucinosis in patients with mixed connective tissue disease in remission; one patient presented the papular form, and the other reticular erythematous mucinosis. These are the first cases of mucinosis described in mixed connective tissue disease. Both cases had skin lesions with no other clinical or laboratorial manifestations, with clinical response to azathioprine in one, and to an association of chloroquine and prednisone in the other.

A mucinose cutânea é um grupo de condições em que há um acúmulo de mucina ou glicosaminoglicanos na pele e seus anexos. É descrita em algumas doenças do tecido conjuntivo, porem nunca em associação com doença mista do tecido conjuntivo. Relatamos dois casos de mucinose cutânea em pacientes com doença mista do tecido conjuntivo em remissão, um apresentava-se sob a forma papular e outro sob a forma reticular eritematosa de mucinose. Estes são os primeiros casos de mucinose descritos na doença mista do tecido conjuntivo. Ambos os casos apresentaram o quadro cutâneo de modo isolado, sem nenhuma outra manifestação clínico-laboratorial, havendo resposta à azatioprina em um e à cloroquina associada a prednisona no outro.

Hipertensión arterial pulmonar asociada a enfermedades del tejido conectivo / Pulmonary arterial hypertension and connective tissue diseases

La clasificación de la hipertensión pulmonar (HP) ha evolucionado a lo largo de los años así como el conocimiento sobre su fisiopatología. Actualmente está definida por una presión arterial pulmonar media igual o mayor a 25 mmHg en reposo medido por cateterismo cardíaco derecho. La hipertensión arterial pulmonar (HAP) incluye un grupo heterogéneo de enfermedades entre las que, además de la HAP idiopática (HAPI) se encuentra la HP asociada a varias condiciones como enfermedades del tejido conectivo (ETC) A pesar de que la HAP asociada a (ETC) se encuentra dentro del mismo grupo que la HAPI y tienen una prevalencia similar, existen diferencias clínicas y epidemiológicas relevantes. Este trabajo intenta actualizar las características epidemiológicas, fisiopatológicas, clínicas y el tratamiento de la HAP asociada a las ETC.

The classification of pulmonary arterial hypertension (PAH) and the knowledge on its physiopathology have evolved over the years. The present definition of pulmonary arterial hypertension is when the tension at rest, measured through right heart catheterization, is 25 or more mm Hg. The pulmonary arterial hypertension includes a heterogeneous group of diseases such as the idiopathic PAH and the PAH associated to connective tissue diseases. Although the PAH associated to connective tissue diseases belongs to the same group of idiopathic PAH and both have a similar prevalence, there are relevant clinical and epidemiological differences. The objective of this paper is to describe the epidemiological, physiopathologic and clinical characteristics and the treatment of the PAH associated to connective tissue diseases.

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0) and geometric mean titer (p = 0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7), seroconversion (68.1% vs. 65.2%, (p = 1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20), skin ulcers (p = 0.48), lupus-like cutaneous disease (p = 0.74), secondary Sjogren syndrome (p = 0.78), scleroderma-pattern in the nailfold capillaroscopy (p = 1.0), lymphopenia #1000/mm³ on two or more occasions (p = 1.0), hypergammaglobulinemia $1.6 g/d (p = 0.60), pulmonary hypertension (p = 1.0) and pulmonary fibrosis (p = 0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94), aldolase (p = 0.73), creatine phosphokinase (p = 0.40) and ribonucleoprotein antibody levels (p = 0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy.

A Case of Long-Segment Barrett's Esophagus with Mixed Connective Tissue Disease / 대한내과학회지

Barrett's esophagus is a metaplasia of the esophageal epithelium of any length, such that normal squamous epithelium is replaced by specialized columnar epithelium with goblet cells. It is important to diagnose and survey Barrett's esophagus because it is believed to be the major risk factor for development of esophageal adenocarcinoma. However, the prevalence of Barrett's esophagus in Korea is low. Mixed connective tissue disease (MCTD) is a systemic disorder in which patients have combinations of the clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis. Although gastroesophageal reflux disease is common in esophageal involvement in MCTD, long-segment Barrett's esophagus in MCTD has not been reported in Korea. We report here a 15 cm-long segment of Barrett's esophagus extending to the proximal esophagus in a female patient who has had MCTD for 2 years, and we review the literature.