Caracterización clínico-radiológica de pacientes con enfermedad pulmonar intersticial y panel de miositis positivo en hospital Santiago Oriente / Clinical-radiological characterization of patients with interstitial lung disease and positive myositis panel at hospital Santiago Oriente

Introducción: Las Enfermedades Pulmonares Intersticiales (EPI) afectan principalmente al intersticio pulmonar, con importante morbimortalidad asociada. Tienen un espectro de posibles etiologías que es cada vez más amplio. Hay una importante causalidad a partir de Enfermedades del Tejido Conectivo (ETC), describiéndose cada vez más casos asociados a Síndrome Antisintetasa, y con diversos patrones radiológicos según serología obtenida, agrupada en "Panel de Miositis" (PaM). El presente estudio de cohorte retrospectiva reúne PaMs realizados en el Hospital Santiago Oriente, correlacionando resultados con manifestaciones clínicas e imagenológicas. Material y Métodos: Se recuperaron 33 PaMs realizados entre 2017 y 2022, y a través de revisión de fichas de los pacientes de quienes provenían las PaMs se consignaron las principales manifestaciones clínicas, imagenológicas y de la serología reumatológica complementaria, estableciendo correlaciones entre múltiples variables. Resultados: Hubo 15 pacientes PaM positivos (45,4%), 8 de ellos (53%) ya contaban con alguna miopatía inflamatoria diagnosticada. Los principales hallazgos clínicos consignados fueron pápulas de Gottron, artritis, eritema heliotropo, Fenómeno de Raynaud y fiebre. El anticuerpo positivo más frecuente fue Ro-52. Se pudo objetivar ANA positivo en 10 casos (66,7%). Se identificó EPI en 66,7% de aquellos con PaM positivo, siendo la Neumonía Intersticial no específica fibrótica con Neumonía en Organización la manifestación más frecuente. No hubo asociación significativa entre manifestaciones imagenológicas y anticuerpos específicos. Se encontró ANA 1/80 en 66,7% de los casos, lo cual no se asoció a mayor riesgo de EPI. Conclusiones: Existe asociación entre varias ETC y las EPI. Destaca la importancia de los hallazgos clínicos para establecer un adecuado índice de sospecha, para dirigir oportunamente el estudio complementario (ej: PaM), y la eventual terapia específica.

Introduction: Interstitial Lung Diseases (ILD) mainly affect the pulmonary interstitium, with significant associated morbidity and mortality. They have a spectrum of possible etiologies that is increasingly broad. There is an important causality from Connective Tissue Diseases (CTD), describing more and more cases associated with Antisynthetase Syndrome, and with different radiological patterns according to the serology obtained, enclosed into "Panel of Myositis" (PaM). This retrospective cohort study gathers PaMs performed at Hospital Santiago Oriente, PaM results are correlated with clinical and imaging manifestations. Material and Methods: 33 PaMs performed between 2017 and 2022 were saved up and by reviewing the clinical records of the patients from whom the PaMs came, their clinical and radiological manifestations and the results of their complementary rheumatological serology were recorded to establish correlations between multiple variables. Results: There were 15 positive PaMs (45.4%), 8 (53%) of them already had some diagnosed inflammatory myopathy. The main clinical findings reported were Gottron's papules, arthritis, heliotrope erythema, Raynaud's phenomenon, and fever. The most frequent positive antibody detected was Ro-52. Positive ANA could be found in 10 cases (66.7%). PID was identified in 66.7% of those with a positive PaM, being non-specific fibrotic Interstitial Pneumonia with Organizing Pneumonia being the most frequent manifestation. There was no significant association between imaging manifestations and specific antibodies. ANA 1/80 was found in 6.7% of the cases, which was not associated with an increased risk of PID. Conclusions: There is association between several CTEs and EPIs. It is necessary to highlight the importance of the clinical findings to establish an adequate index of suspicion, in order to timely direct the complementary study (eg: PaM), and the eventual specific therapy.

Contribución del panel de miositis en el estudio de pacientes con enfermedades pulmonares intersticiales y sospecha de enfermedad del tejido conectivo / Contribution of myositis panel in the study of patients with interstitial lung disease and suspicion of connective tissue disease

INTRODUCCIÓN: La manifestación extramuscular de las miopatías inflamatorias idiopáticas (MII) es la enfermedad pulmonar intersticial (EPI) y el diagnóstico se basa en autoanticuerpos séricos. Los nuevos anticuerpos específicos y asociados a MII han ayudado a identificar nuevas entidades clínicas en el espectro de MII. El objetivo de este estudio es evaluar la contribución diagnóstica de un panel de anticuerpos de miositis (PM) en una cohorte de pacientes chilenos con EPI sin una enfermedad del tejido conectivo (ETC) definitiva. MATERIALES Y MÉTODOS: A partir de enero de 2017 se realizó un panel de miositis a 111 pacientes consecutivos con EPI y sospecha de ETC, pero sin un diagnóstico definitivo a través de otra herramienta diagnóstica, en el programa de Pulmón-Reumatológico del Instituto Nacional del Tórax, Santiago, Chile. Se compararon las características basales clínicas y serológicas de los pacientes que se asociaban más frecuentemente a la probabilidad de tener un panel positivo. RESULTADOS: El PM fue positivo en 56 de 111 pacientes. El síndrome antisintetasa (SAS) fue el diagnóstico más frecuente. Los anticuerpos más frecuentes fueron Ro-52, PM / Scl-75 y Ku. Las variables más frecuentes en el grupo PM(+) fueron la presencia del Raynaud, miositis, manos de mecánico, los anticuerpos Ro y La positivos, la presencia de un patrón combinado de neumonía intersticial inespecífica y neumonía organizada en la tomografía computarizada de tórax. CONCLUSIONES: la incorporación del PM nos ha ayudado a mejorar nuestra precisión diagnóstica en pacientes con EPI / ETC. Presentamos elementos clínicos y serológicos que perfeccionan el rendimiento de la prueba.

INTRODUCTION: The most common extramuscular manifestation of the idiopathic inflammatory myopathies (IIM) is interstitial lung disease (ILD) and the diagnosis is based on serum autoantibodies. The new specific and associated antibodies to IIM have helped to identify new clinical entities in the spectrum of IIM. The objective of this study is to evaluate the diagnostic contribution of a myositis antibodies panel (MP) in a cohort of Chilean patients with ILD without a definitive connective tissue disease (CTD). MATERIALS AND METHODS: Starting on January 2017 we performed a MP to 111 consecutive patients with ILD and suspected CTD but without a definitive diagnosis through another diagnostic tools in the Lung-Rheumatological Program at the "Instituto Nacional del Tórax", Santiago, Chile. The clinical and serological baseline characteristics of the patients that were most frequently associated with the probability of having a positive panel were compared. RESULTS: The MP was positive in 56 of 111 patients. Anti synthetase syndrome (ASS) was the most prevalent diagnosis. The most frequent antibodies were Ro-52, PM/Scl-75 and Ku. The most frequent variables in the positive MP group were the presence of Raynaud's phenomenon, myositis, mechanic's hands, positive Ro and La antibodies and the presence of combined pattern of nonspecific interstitial pneumonia and organizing pneumonia in chest computed tomography scan. CONCLUSIONS: The incorporation of the MP has helped us to improve our diagnostic precision of patients with CTD/ILD. We present clinical and serological elements that refine the performance of the test.

Enfermedad pulmonar intersticial por IgG4 / IgG4-related interstitial lung disease

Las enfermedades relacionadas con inmunoglobulina G4 (IgG4) son un grupo heterogéneo de cuadros clínicos que pueden afectar un solo órgano o tener compromiso sistémico. Se presenta el caso de una mujer de 55 años, internada por un cuadro de tos seca, fiebre, disnea progresiva e insuficiencia respiratoria. La tomografía de tórax evidenció áreas de vidrio esmerilado difusas, patrón reticular y consolidación alveolar. Recibió tratamiento habitual para neumonía de la comunidad y corticoides sistémicos, presentando buena evolución y otorgándose el alta. Al mes se reinterna por estenosis subglótica, progresión de infiltrados pulmonares y aumento del volumen palpebral y de las glándulas submaxilares. Se realizaron biopsias transbronquial y de glándulas salivales que mostraron infiltración por IgG4. También se detectó aumento de los niveles de IgG4 en plasma. Recibió tratamiento con inmunosupresores evolucionando con buena respuesta.

IgG4-related disease is a heterogeneous group of diseases that can affect a single organ or manifest as a systemic disease. We present the case of a 55-year-old female, admitted for dry cough, fever, progressive dyspnea and respiratory failure. Chest CT showed areas of diffuse ground glass, reticular pattern and alveolar consolidation. She received treatment for community acquired pneumonia and systemic corticosteroids with good response. One month later, she was admitted again due to subglottic stenosis, progression of pulmonary infiltrates, and increased palpebral and submaxillary glands volume. Transbronchial and salivary gland biopsies showed infiltration by IgG4. Increased levels of plasma IgG4 were also detected. Immunosuppressive therapy was given with good response.

Dermatomiositis asociada al autoanticuerpo anti-MDA5 / Dermatomyositis associated with anti-MDA5 autoantibody

La dematomiositis es una miopatía inflamatoria idiopática con espectro clínico variable. En los últimos años se ha identificado un número de autoanticuerpos específicos de miositis útiles para el diagnóstico, la clasificación y el pronóstico de las diversas formas de la enfermedad, entre los que se encuentra el anti-MDA5. Este anticuerpo se asocia al desarrollo de úlceras cutáneas, enfermedad intersticial pulmonar rápidamente progresiva, mortalidad temprana y mal pronóstico por lo que la detección del mismo, en un contexto clínico adecuado, plantea la necesidad de un tratamiento inmunosupresor agresivo. Describimos un caso de dermatomiositis hipomiopática, (es decir, con afección muscular leve) que presentaba compromiso cutáneo específico, enfermedad pulmonar intersticial y anticuerpo anti-MDA5 que respondió favorablemente al tratamiento combinado con ciclofosfamida, gamaglobulina y corticoides.

Dematomyositis is an idiopathic inflammatory myopathy with a variable clinical spectrum. In recent years, a number of myositis-specific antibodies have been identified including anti-MDA5, which is us eful for diagnosis, prognosis and classification of the diverse clinical forms of the disease. This antibody is associated with cutaneous ulcers, rapidly progressive interstitial lung disease, early mortality and poor prognosis, so the detection of this antibody in a suitable clinical context, raises the need for an aggressive immunosuppressive treatment. We describe a case of dermatomyositis classified as hypomyopathic (i.e. involving mild muscle weakness), presenting specific skin lesions, interstitial lung disease, and presence of anti-MDA5 antibody that had a favorable response to combined treatment with cyclophosphamide, gamma globulin and corticosteroids.

Anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus

Abstract: Background: The clinical significance of anti-neutrophil cytoplasmic antibodies in patients with new-onset systemic lupus erythematosus, especially in systemic disease accompanied by interstitial lung disease remains to be elucidated. Objectives: This study was designed to investigate the role of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients. Methods: A hundred and seven patients with new-onset SLE were enrolled. Presence of anti-neutrophil cytoplasmic antibodies in the sera was assessed by indirect immunofluorescence as well as enzyme linked immunosorbent assay against proteinase-3 and myeloperoxidase. Clinical features and laboratory parameters of patients were also recorded. All patients were subjected to chest X-ray, chest high-resolution computed tomography and pulmonary function test. Results: Forty-five systemic lupus erythematosus patients (45/107, 42%) were seropositive for anti-neutrophil cytoplasmic antibodies. Compared with anti-neutrophil cytoplasmic antibodies-negative patients, the anti-neutrophil cytoplasmic antibodies-positive patients had significantly higher incidence of renal involvement, anemia, and Raynaud's phenomenon as well as decreased serum level of complement 3/complement 4 and elevated erythrocyte sedimentation rate. In addition, there was a positive correlation between serum anti-neutrophil cytoplasmic antibodies level and disease activity of systemic lupus erythematosus. Furthermore, prevalence of interstitial lung disease in the anti-neutrophil cytoplasmic antibodies -positive patients (25/45, 55.6%) was obviously higher than that in the anti-neutrophil cytoplasmic antibodies-negative patients (15/62, 24.2%). Study limitations: The sample size was limited and the criteria for screening new-onset systemic lupus erythematosus patients might produce bias. Conclusions: The level of anti-neutrophil cytoplasmic antibodies in new-onset systemic lupus erythematosus patients correlates positively with the disease activity and the prevalence of interstitial lung disease.

Caracterización clínica, serológica y patrón radiológico de una cohorte unicéntrica de pacientes con enfermedad pulmonar difusa / Clinical, serological and radiological pattern characterization of a monocentric cohort of patients with diffuse lung disease

Diffuse Lung Disease (DLD) is an important cause of morbidity and mortality, however in Chile we are lacking of epidemiological data on this condition. Our aim is communicate the first report of a prospective registry of DLD patients treated at bronchopulmonary unit of DIPRECA hospital. Methods: Cross-sectional study in patients referred to our bronchopulmonary unit under suspicion of DLD. Diagnosis was confirmed by chest computed tomography and informed consent was approved by patients. Data regarding clinical, serological, pulmonary function tests and echocardiography were collected from 2014 up to date. Results: 30 patients were analysed, their median of age was 76.5 years-old (Interquartile Range 68-80), 56.7% were women, median duration of disease: 4 years (IQR 1-10.6) and 43% has smoking history Most frequent signs and symptoms were crackles (97%), dyspnoea (90%) and cough (57%). Comorbidities: 3% had asthma, 3% chronic obstructive pulmonary disease and 6.7% connective tissue diseases. Radiological findings: 20% had DLD with usual interstitial pneumonia pattern (UIP), 23% DLD possible UIP, 30% DLD inconsistent with UIP, 14% chronic hypersensitivity pneumonitis and 13% nonspecific interstitial pneumonia. Serology: 18% had positive rheumatoid factor of which only one case had rheumatoid arthritis, 67% had positive antinuclear antibodies (ANA), 17% ANCA positive of which only one case of clinical vasculitis. Spirometry was mainly normal (52%) or restrictive (45%). Echocardiography showed pulmonary hypertension mainly mild in 52% of patients. No significant association was found between titles of ANA ≥ 1/320 and gender, smoking or radiological pattern. Conclusions: Our demographic and radiological findings are similar to those reported in literature; however, the highlights in our cohort are the increased frequency of female gender and positive ANA without history or clinical manifestation of connective tissue diseases.

La enfermedad pulmonar difusa (EPD) es causa importante de morbimortalidad; a pesar de esto no tenemos datos epidemiológicos en Chile. Nuestro objetivo es comunicar el primer reporte del registro prospectivo de pacientes con EPD atendidos en la unidad de broncopulmonar del hospital DIPRECA. Métodos: Estudio de corte transversal en pacientes derivados alpoliclínico broncopulmonar del hospital DIPRECA por sospecha de EPD. En caso de confirmación diagnóstica por tomografía computada de tórax y consentimiento informado aprobado por los pacientes, se compilaron datos clínicos, serológicos, pruebas de función pulmonar y ecocardiografía, desde 2014 hasta la fecha. Resultados: Se analizaron 30 pacientes la mediana de su edad fue 76,5 años (rango intercuartílico 68-80), 56,7% eran mujeres, duración mediana de la enfermedad: 4 años (RIC 1-10,6)y 43% con antecedentes de tabaquismo. Los síntomas y signos más frecuente fueron crujidos (97%), disnea (90%) y tos (57%). Comorbilidades: 3% tenía asma, 3% enfermedad pulmonar obstructiva crónica y 6,7% enfermedades del tejido conectivo. Hallazgos radiológicos: 20% tenía EPD con patrón de neumonía intersticial usual (UIP), 23% EPD posible UIP, 30% EPD inconsistente con UIP, 14% neumonitis por hipersensibilidad crónica y 13% neumonía intersticial no específica. Serología: 18% tenía factor reumatoide positivo de ellos sólo uno de los casos tenía artritis reumatoide, el 67% tenía anticuerpos antinucleares (ANA) positivos, 17% ANCA positivo de ellos sólo un caso tenía historia de vasculitis clínica. La espirometría fue mayoritariamente normal (52%) o restrictiva (45%). Ecocardiografía detectó hipertensión pulmonar mayoritariamente leve en 52% de los pacientes. No se encontró asociación significativa entre los títulos de ANA ≥ 1/320 en relación a género, tabaquismo o patrón radiológico. Conclusiones: Nuestros hallazgos demográficos y radiológicos son similares a los de la literatura; sin embargo, destaca en nuestra cohorte la mayor frecuencia de género femenino y ANA positivos sin historia o manifestación clínica de enfermedades del tejido conectivo.

Serum Clara cell 16-kDa protein levels and lung impairment in systemic sclerosis patients / Níveis séricos de proteína de células de Clara de 16 kDa e comprometimento pulmonar em pacientes com esclerose sistêmica

ABSTRACT Objective: To assess clinical utility of serum Clara cell 16-kDa protein measurements in relation with staging system for systemic sclerosis associated interstitial lung disease. Materials and methods: Serum levels of Clara cell 16-kDa protein were determined by ELISA in 28 systemic sclerosis patients and 30 healthy controls, and correlated with staging system for systemic sclerosis associated interstitial lung disease in systemic sclerosis patients. Lung involvement was assessed functionally (body plethysmography, diffusing capacity of the lung for carbon monoxide) and radiologically (an average disease extent on high resolution computed tomography of the lungs) in SSc patients. Results: We observed statistically significant differences in serum Clara cell 16-kDa protein levels between systemic sclerosis patients and healthy controls only in non-smokers. However, serum Clara cell 16-kDa protein concentrations were significantly elevated in patients with high resolution computed tomography extent >20% in comparison to patients with high resolution computed tomography extent <20% (p = 0.01). They correlated positively with average disease extent on high resolution computed tomography (p = 0.04), an extent of a reticular pattern on high resolution computed tomography (p < 0.01), and negatively with a total lung capacity (p = 0.03) and the results of the 6-min walk test (p < 0.01). Conclusions: Clara cell 16-kDa protein levels can be considered as a supplemental serum biomarker for systemic sclerosis associated interstitial lung disease.

RESUMO Objetivo: Avaliar a utilidade clínica das medições séricas da proteína de células de Clara de 16-kDa (CC16) em relação ao sistema de estadiamento para doença pulmonar intersticial associada a esclerose sistêmica (DPI-ES). Materiais e métodos: Foram determinados os níveis séricos de CC16 por ELISA em 28 pacientes com ES e 30 controles saudáveis e correlacionados com o sistema de estadiamento para DPI-ES em pacientes com ES. O envolvimento pulmonar foi avaliado funcionalmente (pletismografia corporal, capacidade de difusão de monóxido de carbono) e radiologicamente (extensão média da doença na tomografia computadorizada de alta resolução dos pulmões, TCAR) em pacientes com ES. Resultados: Foram encontradas diferenças estatisticamente significativas nos níveis séricos de CC16 entre pacientes com ES e controles saudáveis apenas em não tabagistas. No entanto, as concentrações séricas de CC16 eram significativamente elevadas em pacientes com extensão > 20% na TCAR em comparação com pacientes com extensão < 20% na TCAR (p = 0,01). Os níveis séricos de CC16 se correlacionaram positivamente com a extensão média da doença na TCAR (p = 0,04) e com a extensão de padrão reticular na TCAR (p < 0,01) e negativamente com a capacidade pulmonar total (CPT) (p = 0,03) e com os resultados do teste de caminhada de seis minutos (p < 0,01). Conclusões: Os níveis de CC16 podem ser considerados como biomarcadores séricos suplementares para a DPI-ES.

Inmunodeficiencia común variable: Epidemiología y manifestaciones clínicas en 69 pacientes / Common variable immunodeficiency: Epidemiology and clinical manifestations in 69 patients

La inmunodeficiencia común variable (IDCV) se caracteriza por una alteración en la producción de anticuerpos y una mayor susceptibilidad a infecciones por bacterias extracelulares capsuladas, principalmente del tracto respiratorio. Analizamos las características clínicas de 69 pacientes, evaluados en un período de 10 años en tres centros de la ciudad de Buenos Aires. Al inicio del estudio se encontraban en seguimiento 14 pacientes y al finalizar 60; la mayoría fueron derivados por infecciones o hipogammaglobulinemia, y casi la mitad con diagnóstico establecido de inmunodeficiencia. Sesenta y cinco (94.2%) pacientes presentaron infecciones por gérmenes capsulados, cuatro (6.1%) sepsis y dos tuberculosis. La edad promedio de comienzo de los síntomas infecciosos fue de 18.1 años, la edad promedio al momento del diagnóstico fue de 29.6 años y el retraso diagnóstico de 11.9 años. En 41 (59.4%) pacientes se registró el antecedente de diarreas recurrentes o crónicas. En 22 (31.9%) se diagnosticaron 13 enfermedades autoinmunes, siendo las más frecuentes las hematológicas y el hipotiroidismo. Ocho pacientes tuvieron linfoproliferación policlonal histológica, cuatro (5.8%) como enfermedad granulomatosa de hígado, laringe y piel, y cuatro como neumonía intersticial linfoidea (NIL). Diecinueve (27.5%) pacientes presentaron esplenomegalia y 23/57 (40.3%) imágenes sugestivas de procesos granulomatosos o linfocíticos en la TAC de tórax (incluidos los 4 con NIL). Tres (4.3%) pacientes desarrollaron linfoma B, cuatro (5.8%) adenocarcinoma de estómago y uno cáncer de mama. El estudio tuvo una mediana de seguimiento de 54 meses, rango 1-353 y durante el período del mismo murieron cuatro pacientes (5.8%).

Common variable immunodeficiency (CVID) is characterized by an impaired antibody production and an increased susceptibility to recurrent infections of the respiratory tract, mainly by extracellular encapsulated bacteria. We analyzed the clinical characteristics of 69 patients evaluated over a period of 10 years at three centers in the city of Buenos Aires. At the onset of the study 14 patients were on follow up, and at its end the number of patients reached to 60. Most of them consulted for infection or hypogammaglobulinemia and nearly half had an established diagnosis of immunodeficiency. Sixty-five (94.2%) patients had infections by encapsulated bacteria, four (6.1%) sepsis and two tuberculosis. The average age of onset of infectious symptoms was 18.1 years; the average age at diagnosis was 29.6 years and the delay to diagnosis 11.9 years. Forty one (59.4%) patients reported a history of recurrent or chronic diarrhea. In 22 (31.9%) 13 autoimmune diseases were diagnosed, being the most frequent the hematological disorders and hypothyroidism. Eight patients had histological polyclonal lymphoproliferation, four (5.8%) with granulomatous disease affecting the liver, the larynx and/or the skin; and four as lymphoid interstitial pneumonitis (LIP). Nineteen (27.5%) patients had splenomegaly and 23/57 (40.3%) images suggestive of lymphocytic or granulomatous processes (including the 4 with LIP) in the chest CT. Three (4.3%) patients developed B cell lymphoma, four (5.8%) stomach adenocarcinoma and one breast cancer. The study had a median follow-up of 54 months, range 1-353 and four patients (5.8%) died during the follow up.

Síndrome Antisintetasa / Antisynthetase syndrome

El síndrome antisintetasa es una entidad poco frecuente, incluida dentro del grupo de las miopatías inflamatorias idiopáticas. Se caracteriza por la presencia de anticuerpos antisintetasa, fiebre, miositis, enfermedad pulmonar intersticial, poliartritis, fenómeno de Raynaud y manos de mecánico.

The antisynthetase syndrome is a rare condition that has been included in the group of idiopatic inflammatory skeletal muscle disease. The presence of antisynthetase autoantibody, fever, myositis, intersticial lung disease, polyarthritis, Raynaud´s phenomenon and “mechanic´s hands” represent the main characteristics of antisynthetase syndrome.

Doença pulmonar intersticial relacionada a miosite e a síndrome antissintetase / Myositis-related interstitial lung disease and antisynthetase syndrome

Em pacientes com miosite, é comum o comprometimento pulmonar, e a presença de anticorpos anti-aminoacil-RNAt sintetase (anti-ARS) é preditora da presença ou do desenvolvimento de doença pulmonar intersticial (DPI). Uma entidade clínica distinta - a síndrome antissintetase - é caracterizada pela presença de anticorpos anti-ARS, miosite, DPI, artrite, fenômeno de Raynaud e "mãos de mecânico". O mais comum anticorpo anti-ARS é o anti-Jo-1. Anticorpos anti-ARS mais recentemente descritos podem conferir um fenótipo que é distinto daquele de pacientes com positividade para anti-Jo-1, sendo caracterizado por uma menor incidência de miosite e uma maior incidência de DPI. Nos pacientes com DPI relacionada à síndrome antissintetase, a resposta a medicações imunossupressoras é em geral favorável.

In patients with myositis, the lung is commonly involved, and the presence of anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies marks the presence or predicts the development of interstitial lung disease (ILD). A distinct clinical entity-antisynthetase syndrome-is characterized by the presence of anti-ARS antibodies, myositis, ILD, fever, arthritis, Raynaud's phenomenon, and mechanic's hands. The most common anti-ARS antibody is anti-Jo-1. More recently described anti-ARS antibodies might confer a phenotype that is distinct from that of anti-Jo-1-positive patients and is characterized by a lower incidence of myositis and a higher incidence of ILD. Among patients with antisynthetase syndrome-related ILD, the response to immunosuppressive medications is generally, but not universally, favorable.

Imunofenotipagem e rearranjo gênico em doenças pulmonares linfocíticas e linfoproliferativas / Immunophenotyping and gene rearrangement analysis in lymphoid/lymphoproliferative disorders of the lungs

OBJETIVO: Determinar a utilidade, na prática rotineira, da análise da clonalidade dos linfócitos T e B nos tecidos pulmonares por reação em cadeia da polimerase no diagnóstico das doenças linfoproliferativas pulmonares. MÉTODOS: Avaliaram-se, mediante análise imunohistoquímica e rearranjo molecular dos genes, 8 casos de pneumonia intersticial linfocítica (PIL) e 7 casos de doenças linfoproliferativas pulmonares. RESULTADOS: Todos os 8 casos de PIL expressaram imunocoloração moderada a forte para CD3, em contraste com apenas 2 casos de linfoma e 1 caso de pseudolinfoma. Rearranjo gênico foi detectado em 4 de 8 casos de PIL, o que mudou o diagnóstico de PIL para linfoma, indicando, assim, a importância da detecção de rearranjo gênico em casos de PIL. Nesta situação, rearranjo gênico usando-se os pares de primers VH/JH e Vgama11/Jgama12 foi detectado em 3 e 1 casos de PIL, respectivamente, e não foram detectadas anormalidades gênicas usando-se as pares Dbeta1/Jbeta2 e Vgama101/Jgama12. Uma associação positiva foi detectada entre a intensidade de imunoexpressão CD20 e CD68 e rearranjo gênico usando-se o par de primers VH/JH. Antes do rearranjo gênico, 4 pacientes com PIL morreram rapidamente, enquanto que, após o rearranjo gênico, apenas 1 paciente com PIL morreu. CONCLUSÕES: A detecção de células B e T monoclonais por imunofenotipagem e reação em cadeia da polimerase mostrou impacto no diagnóstico de linfomas pulmonares em pacientes previamente diagnosticados com PIL. Portanto, imunofenotipagem e reação em cadeia da polimerase devem ser incluídas como métodos de 'padrão ouro' na rotina diagnóstica.

OBJECTIVE: To determine the usefulness, in routine practice, of using polymerase chain reaction to analyze B and T lymphocyte clonality in pulmonary tissue as a tool for the diagnosis of pulmonary lymphoproliferative disorders. METHODS: Immunohistochemistry and molecular gene rearrangement analysis were performed in order to assess 8 cases of lymphoid interstitial pneumonia (LIP) and 7 cases of pulmonary lymphoproliferative disorders. RESULTS: All 8 cases of LIP presented moderate to strong immunostaining for CD3, compared with only 2 cases of lymphoma and 1 case of pseudolymphoma (p = 0.02). Gene rearrangement was detected in 4 of the 8 cases, which changed the diagnosis from LIP to lymphoma, showing the importance of gene rearrangement detection in cases of LIP. In this situation, gene rearrangement using the VH/JH and Vgamma11/Jgamma12 primer pairs was detected in 3 cases and 1 case, respectively, and no gene abnormalities were found using the Dbeta1/Jbeta2 and Vgamma101/Jgamma12 primer pairs in any of the cases. A significant positive association was found between the intensity of CD20 and CD68 expression and gene rearrangement using the VH/JH primer pair. Prior to the gene rearrangement, 4 patients with LIP died quickly, whereas only one patient with LIP died after the gene rearrangement. CONCLUSIONS: Detection of monoclonal B and T cells by immunophenotyping and polymerase chain reaction had an impact on the diagnosis of pulmonary lymphomas in patients previously diagnosed with LIP. Therefore, immunophenotyping and polymerase chain reaction should be used as 'gold standard' techniques in routine practice.

Autopsy-proven causes of death in lungs of patients immunocompromised by secondary interstitial pneumonia

PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28 percent) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary...

OBJETIVO: Apresentar as associações mais freqüentes encontradas em autópsias de pacientes imunossuprimidos que desenvolveram pneumonia intersticial secundária bem como o risco de óbito (Odds Ratio) de desenvolver PIS associada à causa da imunossupressão. MÉTODO: De janeiro de 1994 a março de 2004, 17000 autópsias foram realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A partir da revisão dos laudos patológicos foram selecionados 558 destas autópsias (3,28 por cento) de pacientes com 15 anos de idade ou mais, com alguma doença de base que desenvolveu um infiltrado pulmonar radiologicamente difuso durante o curso da hospitalização e que depois foi para óbito com pneumonia intersticial secundária (broncopneumonia, pneumonia lobar, pneumonia intersticial, dano alveolar difuso, doença pulmonar recorrente, doença pulmonar induzida por drogas, edema pulmonar cardiogênico e embolismo pulmonar). As lâminas histológicas foram revisadas por patologistas experientes para confirmar ou não a presença de pneumonia intersticial secundária. A análise estatística incluiu o "Teste exato de Fisher" para verificar associação entre a histolopatologia e causa de imunocomprometimento; e regressão logística para predizer o risco de óbito por achados histológicos específicos para cada variável independente do modelo. RESULTADOS: A pneumonia intersticial secundária foi representada histológicamente por pneumonite intersticial difusa variando de características não especificas leves (n=213) ao padrão histológico de dano alveolar difuso (n=273). A principal causa de imunossupressão nos pacientes com dano alveolar difuso foi sepse (136 casos), neoplasia (113 casos), diabetes melito (37 casos) e transplantados (37 casos). O maior risco de morte por edema pulmonar foi encontrado nos pacientes com carcinoma de cólon. Da mesma forma, nos pacientes com câncer pulmonar ou cachexia ocorreu um alto risco de morte (OR=3.6; OR=2.6, respectivamente)...

Nonhomogeneous immunostaining of hyaline membranes in different manifestations of diffuse alveolar damage / Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (a-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65 percent ± 3.24 percent), while extrapulmonary diffuse alveolar damage (9.52 percent ± 3.64 percent) and idiopathic diffuse alveolar damage (7.34 percent ± 2.11 percent) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36 percent ± 3.12 percent), extrapulmonary (16.12 percent ± 4.58 percent), and idiopathic (13.74 ± 4.20 percent) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12 percent ± 6.25 percent) than extrapulmonary diffuse alveolar damage...

OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a) dano alveolar difuso pulmonar (DADp) (n=8) constituído por casos de pneumonia, (b) dano alveolar difuso extrapulmonar (DADexp) (n=9) constituído por casos de sepse e choque séptico e (c) dano alveolar difuso idiopático (DADi) (n=9) constituído por casos idopáticos (ou pneumonia intersticial aguda). As características das membranas hialinas do padrão histológico de dano alveolar difuso foram examinadas usando vários tipos de anticorpos. Os anticorpos usados foram surfactante apoproteina A (SP-A), anti-citokeratina 7 (CK7), citokeratina 8 (CK8), alfa actina de músculo liso (a-SMA), citokeratina AE1/AE3 (AE1/AE3) e antígeno relacionado ao fator VIII (Fator VIII). RESULTADOS: Observaram-se aumentos maiores da quantidade de membrana hialina no dano alveolar difuso pulmonar (12.65 ± 3.24 por cento), intermediários no dano alveolar difuso extrapulmonar (9.52 ± 3.64 por cento) e baixos no dano alveolar difuso idiopático (7.34 ± 2.11 por cento) respectivamente, esta diferencia foi estatística significante entre o dano alveolar difuso pulmonar e o dano alveolar difuso idiopático (p<0.05). Não se encontrou significância estatística para a quantidade de imunomarcação de Sp-A nos grupos de dano alveolar difuso pulmonar (15.36 ± 3.12 por cento), extrapulmonar (16.12 ± 4.58 por cento) e idiopático (13.74 ± 4.20 por cento). Com relação ao Fator VIII, nós encontramos maiores aumentos da imunomarcação da membrana hialina no grupo dano alveolar difuso idiopático (14.12 ± 6.25 por cento) do que no dano alveolar difuso extrapulmonar (3.93 ± 2.86 por cento), com significância estatística (p<0.001). Da mesma...

Neumonía intersticial usual en Enfermedad de Still del adulto / Usual Interstitial Pneumonia in adult Still’ disease

La Enfermedad de Still del adulto (AOSD) es un desorden multisistémico inflamatorio de etiología desconocida, caracterizado por fiebre alta en espigas, brote cutáneo de color salmón evanescente, artralgias o artritis, hepatoesplenomegalia, linfadenopatías y malestar de garganta, entre otras. No es infrecuente que la enfermedad de Still comprometa otros órganos como el hígado, los riñones, la médula ósea y de manera menos frecuente los pulmones. El compromiso pulmonar varía según las diferentes series entre un 30 a 40 por ciento (0 a 53 por ciento) manifestándose como un simple derrame pleural hasta síndrome de dificultad respiratorio agudo. Nosotros presentamos un caso asociado a enfermedad pulmonar intersticial difusa y revisamos la literatura sobre este tipo de compromiso

Spectrum of anti-neutrophil cytoplasmic antibodies in patients with pulmonary tuberculosis overlaps with that of Wegener's granulomatosis.

BACKGROUND AND OBJECTIVES: Mycobacterial infections are known to induce the development of autoantibodies and a few of these antibodies are also known to be diagnostic markers for some other diseases and it is uncertain whether these autoantibodies play a role in the pathogenesis of autoimmune disorders. This study was undertaken to determine the prevalence of autoantibodies like anti-neutrophil cytoplasmic antibodies (ANCA), anti-nuclear antibodies (ANA), anti-double stranded antibodies (anti-dsDNA) and anti-histone antibodies (AHA)in pulmonary Tuberculosis. MATERIALS & METHODS: Seventy consecutive pulmonary TB patients, 30 patients of interstitial lung disease and 100 normal individuals were studied. ANCA and ANA were detected by indirect immunofluorescence test (IIF). Anti-dsDNA and AHA were tested by ELISA. RESULTS: ANCA was detected in 30% cases, and of these 52.4% showed perinuclear pattern (p-ANCA), 38.1% cytoplasmic (c-ANCA) and 9.5% showed an "atypical" pattern. ANCA specificities by ELISA revealed that, 47.6% had anti-Myeloperoxidase (anti-MPO), 28.6% had anti-Proteinase3 (anti-PR3) and 19.1% had anti-Lactoferrin (anti-LF) antibodies. ANA and AHA were present in 24.3% and 21.4% cases respectively whereas anti-ds DNA antibodies were absent. Normal controls showed 4% and 2% positivity for ANA and ANCA whereas disease control group of ILD showed 7% of ANA and ANCA posititivy. CONCLUSION: The presence of autoantibodies in TB patients could have a multifactorial etiology. Clinically relevant is the presence of anti-PR3 antibodies. This finding along with pulmonary and renal manifestations could lead to a false diagnosis of Wegener's granulomatosis or vice versa because these autoantibodies may be present in both diseases.

Experiencia clínica de la utilidad del lavado broncoalveolar en pediatría / Bronchoalveolar lavage in children

Introducción: Se ha descrito que el lavado broncoalveolar (LBA) tiene utilidad en la determinación etiológica de pacientes con neumonías de evolución inhabitual y en pacientes inmunodeprimidos. La información publicada es en su mayoría extranjera, existiendo escasa información en Chile. Objetivo: revisar restrospectivamente la experiencia clínica de LBA realizados en el servicio de pediatría del Hospital Clínico de la Universidad Católica entre abril 1993 y julio 2001. pacientes y métodos: Se utilizó un fibrobroncoscopio olympus de 3,6 mm de diámetro externo, con una vieocámara sony DXC-C1 utilizando para el LBA 4 a 6 alícuotas de 1 cc/kg (volumen máximo: 15 ml) de suero fisiológico al 0,9 por ciento c/u, tomando muestras de secreción bronquial, las que fueron enviadas para estudio viral, bacteriológico, tuberculosis, hongos y pneumocystis carinii. Resultados: se realizaron un total de 97 LBA, analizándose el resultado de 82 LBA de 74 pacientes. hubo 60 LBA en inmunosuprimidos, cuyos diagnósticos fueron: neumonía 15, neumonía intersticial 9, neumonía con atelectasia 3, distrés respiratorio agudo 3. de estos 30 LBA, hubo un total de 14 resultados positivos (46,6 por ciento), 10 para germen patógeno (33,3 por ciento); CMV 5, reacción de polimerasa en cadena (PCR) (+) pneumocystis carinii 2, CMV + pneumocystis carinii2. De los 52 LBA en inmunocompetentes los diagnïsticos fueron de neumonía con o sin atelectasia 32, sospecha de hemosiderosis 7, tuberculosis 4, bronquiectasias 3 y 6 misceláneos. Hubo un total de 21 de 44 cultivos positivos (47,7 por ciento), aislándose haemophilus influenzae en 7, pseudomona aeruginosa 4, CMV 3 y staphylococcus aureus 2. El LBA cambió la conducta en 29 pacientes (35,3 por ciento) y ésta incluyó: cambio de terapia antibiótica en 14 pacientes, inicio de ganciclovir en 7. Conclusiones: el LBA es una herramienta de gran ayuda en el paciente que presenta una neumonía inhabitual, en especial en inmunodeprimidos, ya que al determinar un diagnóstico preciso nos permite una elección adecuada de tratamiento

Neumonitis inducida por el rubulavirus porcino / Pneumonitis induced by pork rubulavirus

Introducción: El rubulavirus porcino es un virus miembro de la familia Paramixoviridae, subfamilia paramixovirinae y género Rubulavirus. Este virus posee gran homología en la secuencia de nucleótidos y aminoácidos con los virus de las paperas, virus símicos y virus de la parinfluenza 2 y 4. El rubulavirus porcino es responsable de la enfermedad del ojo azul que afecta a cerdos de todas las edades y provoca alteraciones reproductivas, neurológicas y respiratorias. Objetivo: En el presente trabajo identificamos las principales lesiones pulmonares que provoca la infección experimental de cerdos con el rubulavirus porcino. Materiales y métodos: Los animales fueron inoculados por vía intranasal y sacrificados en diferentes tiempos postinfección. En cada tiempo postinfección se analizaron las lesiones macroscópicas y microscópicas, se determinó el título de anticuerpos, y se realizó el aislamiento viral de diversos tejidos. Resultados: Se demostró que el rubulavirus porcino induce una neumonitis intersticial con un infiltrado mononuclear, características de infecciones ocasionadas por paramoxovirus como el virus de las paperas o el virus del sarampión. El aislamiento viral fue mayor en el día cinco postinfección, de manera interesante se logró recuperar el virus principalmente en la tonsila, tráquea y pulmón. Discusión: Con base en estos resultados, este artículo propone a este virus como un modelo experimental para estudiar la patología y respuesta inmune en infecciones causadas por paramixovirus