Pulmonary sarcoidosis with arterial involvement

Necrotizing sarcoid granulomatosis (NSG) is a rare and under-recognized cause of granulomatous disease, described as a variant of typical nodular sarcoidosis. It can be asymptomatic when the patient has a single pulmonary nodule or may be accompanied by cough, fever, and dyspnea, or even symptoms due to the involvement of other organs such as the eyes, liver, and central nervous system. The histopathological analysis is essential for the differential diagnosis of other infectious and non-infectious causes of granuloma and to determine the appropriate treatment. NSG is characterized by the presence of a granuloma with extensive coagulative necrosis associated with the occurrence of vasculitis. We present the case of a patient diagnosed with NSG who had an unusual outcome with recurrent pulmonary thromboembolisms followed by hemodynamic instability and death.

Signos radiológicos: el signo de la galaxia / Radiology signs: the galaxy sign

El signo de la galaxia representa una lesión tipo masa, compuesta por innumerables nódulos granulomatosos coalescentes, más concentrados en el centro que en la periferia. Inicialmente se describió en paciente con sarcoidosis, y se denominó el signo de la galaxia sarcoidea. Actualmente se sabe que puede estar presente en otras entidades como la tuberculosis, el cáncer pulmonar y la fibrosis pulmonar masiva de las neumoconiosis. Es importante su identificación y adecuada interpretación, dado que en asociación con otros signos tomográficos permite una orientación al diagnóstico de sarcoidosis.

The galaxy sign represents a mass-like lesion, composed of innumerable coalescing granulo-matous nodules, more concentrated in the center than at the periphery. It was initially described in patients with sarcoidosis, and was referred to as the "sarcoid galaxy" sign. It is now known to be present in other entities such as tuberculosis, lung cancer and the pulmonary fibrosis mass of pneumoconiosis. Its identification and adequate interpretation is important, given that in association with other tomographic signs it allows an orientation toward the diagnosis of sarcoidosis.

Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar / Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.

OBJECTIVE: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. METHODS: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. RESULTS: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). CONCLUSIONS: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Two cases of thyroid sarcoidosis presentation as painful, recurrent goiter in patients with Graves' disease / Dois casos de sarcoidose na tireoide com apresentação na forma de bócios recorrentes dolorosos em pacientes com doença de Graves

Sarcoidosis rarely involves the thyroid gland. Pain in the thyroid gland area was only sporadically reported in patients suffering from this disease. The aim of this paper is to report and discuss the cases of two female patients with Graves' disease who presented painful, rapidly growing, recurrent goiters (after strumectomy in their early adult lives). Invasive treatment was applied and sarcoidosis was revealed histologically. The first patient suffered from dysphagia and dyspnoea due to large goiter; skin lesions were present as well. Sarcoidosis was diagnosed in histological examination of the thyroid tissue specimens. Steroid treatment was ineffective; thus, the thyroid was removed. Two years later thyroid sarcoidosis recurred as a painful goiter and surgical treatment was applied once again. In the second case, thyroid ultrasound findings suggesting malignancy, and prompted the decision to perform thyroidectomy despite the fact that FNAB (fine needle aspiration biopsy) revealed cells indicative of a "granulomatous disease in the post-resection scar" and results of the thorax high-resolution computed tomography scan suggested pulmonary sarcoidosis. Pathological examination confirmed sarcoidosis. However, a papillary cancer focus was also found.

A sarcoidose raramente envolve a glândula tireoide, e apenas esporadicamente foi relatada dor na região da glândula em pacientes que sofrem dessa doença. O objetivo deste trabalho é relatar e discutir os casos de duas mulheres que apresentavam bócios dolorosos, de rápido crescimento e recorrentes (após tireoidectomia na adolescência). Foi usado um tratamento invasivo e a sarcoidose foi revelada pelos achados histológicos. A primeira paciente sofria de disfagia e dispneia em decorrência de um grande bócio; lesões cutâneas também estavam presentes. A sarcoidose foi diagnosticada em um exame histológico das amostras de tecido da tireoide. O tratamento com esteroides foi ineficaz; foi feita assim a ressecção da glândula. Dois anos depois, houve recidiva da sarcoidose da tireoide como um bócio doloroso, e o tratamento cirúrgico foi feito mais uma vez. No segundo caso, os resultados do ultrassom da tireoide sugeriam malignidade e levaram à decisão de se realizar a tireoidectomia, apesar de as células de PAAF indicarem uma doença granulomatosa na cicatriz pós-ressecção e os resultados da tomografia computadorizada de alta resolução de tórax sugerirem sarcoidose pulmonar. O exame histopatológico da glândula revelou sarcoidose. Entretanto, também foi encontrado um foco de câncer papilar.

Immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in an HIV-infected patient: an immunohistochemical study

Sarcoidosis has been rarely described in literature as a cause of interstitial pulmonary disease associated with AIDS. This study reports a case of immune reconstitution inflammatory syndrome associated with pulmonary sarcoidosis in a patient with a history of previous pulmonary tuberculosis concomitant with HIV infection. Results of the immunohistochemical study of samples from the resected right lower lobe are described. Pathological findings suggest a role of Th1, Th2 and Th17 response in IRIS associated sarcoidosis.

Características epidemiológicas de pacientes com sarcoidose na cidade do Rio de Janeiro / Epidemiological characteristics of sarcoidosis patients in the city of Rio de Janeiro, Brazil

OBJETIVO: Analisar as características epidemiológicas de pacientes com sarcoidose na cidade do Rio de Janeiro. MÉTODOS: Estudo descritivo, caso-controle, envolvendo 100 pacientes com sarcoidose acompanhados no Hospital Universitário Pedro Ernesto, localizado na cidade do Rio de Janeiro, entre 2008 e 2010. O diagnóstico de sarcoidose foi baseado em critérios clínicos, radiográficos, laboratoriais e histopatológicos. RESULTADOS: A doença predominou em mulheres (65 por cento), na faixa de 35-40 anos (variação: 7-69 anos), embora houvesse um segundo pico na população de aproximadamente 55 anos. A dispneia foi o sintoma mais comum (47 por cento), assim como o achado radiográfico de comprometimento pulmonar e linfonodal (estágio II; 43 por cento), seguido por estágio III (20 por cento), estágio 1(19 por cento), estágio 0 (15 por cento) e estágio IV (3 por cento). Nenhum paciente apresentou derrame pleural ou baqueteamento digital no diagnóstico. O PPD foi não reator em 94 pacientes. Os achados espirométricos no diagnóstico foram normais em 61 pacientes; indicativos de distúrbio ventilatório obstrutivo, em 21; e indicativos de distúrbio ventilatório restritivo, em 18. Os sítios de biópsia mais comuns foram os pulmões (principalmente por broncoscopia) e a pele, que confirmaram o diagnóstico em 56 por cento e 29 por cento dos casos, respectivamente. O tratamento com prednisona foi iniciado em 75 por cento dos pacientes e mantido por mais de 2 anos em 19,7 por cento. CONCLUSÕES: Este estudo corrobora vários achados relatados em outros estudos sobre as características epidemiológicas de pacientes com sarcoidose.

OBJECTIVE: To analyze the epidemiological characteristics of sarcoidosis patients in the city of Rio de Janeiro, Brazil. METHODS: A descriptive, case-control study involving 100 sarcoidosis patients under outpatient treatment between 2008 and 2010 at the Pedro Ernesto University Hospital, located in the city of Rio de Janeiro, Brazil. The diagnosis of sarcoidosis was based on clinical, radiological, biochemical, and histopathological criteria. RESULTS: There was a predominance of females in the 35-40 year age bracket (range, 7-69 years), who accounted for 65 percent of the sample, although there was a second peak at approximately 55 years of age. The most common symptom was dyspnea (in 47 percent), and the most common radiological findings were pulmonary and lymph node involvement (stage II; in 43 percent), followed by stage III (in 20 percent), stage I (in 19 percent), stage 0 (in 15 percent), and stage IV (in 3 percent). No pleural effusion or digital clubbing was observed at diagnosis. The tuberculin skin test was negative in 94 patients. Spirometric findings at diagnosis were normal in 61 patients; indicative of obstructive lung disease in 21; and indicative of restrictive lung disease in 18. The most common biopsy sites were the lungs (principally by bronchoscopy) and the skin, the diagnosis being confirmed by biopsy in 56 percent and 29 percent of the cases, respectively. Treatment with prednisone was initiated in 75 percent of the patients and maintained for more than 2 years in 19.7 percent. CONCLUSIONS: This study corroborates the findings of previous studies regarding the epidemiological characteristics of sarcoidosis patients.

Aspectos tomográficos e anatomopatológicos da sarcoidose pulmonar / Tomographic and pathological findings in pulmonary sarcoidosis

OBJETIVO: Analisar os aspectos radiológicos observados nas tomografias computadorizadas de alta resolução de pacientes com sarcoidose e fazer a correlação com os achados anatomopatológicos. MATERIAIS E MÉTODOS: Foram revistos os aspectos radiológicos observados nas tomografias computadorizadas de alta resolução de dez pacientes com sarcoidose e feita correlação com material obtido de biópsias cirúrgicas ou necrópsias de quatro desses pacientes. RESULTADOS: O aspecto mais frequentemente observado foi o de nódulos, com distribuição perilinfática, predominando ao longo das bainhas broncovasculares e da superfície pleural, com nódulos subpleurais e cissuras nodulares. Outros achados menos comuns foram as opacidades em vidro fosco e o espessamento de septos interlobulares. CONCLUSÃO: Em geral, todos esses achados corresponderam, anatomopatologicamente, ao acúmulo de granulomas nessas regiões.

OBJECTIVE: To analyze radiological findings observed at high-resolution computed tomography in patients with sarcoidosis, and establishing their correlation with pathological findings. MATERIALS AND METHODS: High-resolution computed tomography findings in ten patients with sarcoidosis were reviewed and correlated with findings in specimens obtained by surgical biopsy or at necropsy of four of such patients. RESULTS: The most frequently observed finding was presence of nodules with perilymphatic distribution, predominating along bronchovascular sheaths and pleural surface, with subpleural nodules and nodular scissurae. Other less frequent findings were ground-glass attenuation and interlobular septa thickening. CONCLUSION: In general, all the mentioned findings demonstrated anatomopathological correlation with development of granulomas in these regions.

Sarcoidosis pulmonar y gástrica: caso clínico / Pulmonary and gastric sarcoidosis: report of one case

We report a 66 year-old woman with a history of pulmonary sarcoidosis, diagnosed with a lung biopsy in 1993 and treated with prednisone for 2 years. She presented at our institution in 1999 with a stage IV disease and important functional and clinical impairment. A bronchial biopsy disclosed non caseating granulomas. Tuberculosis was intensively studied and persistently negative. Due to frequent nausea and vomiting an endoscopic gastric biopsy was performed which revealed non caseating granulomas involving the gastric mucosa. There was no evidence of Helicobacter pylori and stains for fungi and acid-fast bacilli were negative. Treatment with prednisone relieved digestive symptoms, although a control biopsy of the gastric mucosa revealed persistence of non caseating granulomas. Both lung stage IV and gastric sarcoidosis are uncommon forms of the disease.

Typical and Atypical Manifestations of Intrathoracic Sarcoidosis

Sarcoidosis is a systemic disorder of unknown cause that is characterized by the presence of noncaseating granulomas. The radiological findings associated with sarcoidosis have been well described. The findings include symmetric, bilateral hilar and paratracheal lymphadenopathy, with or without concomitant parenchymal abnormalities (multiple small nodules in a peribronchovascular distribution along with irregular thickening of the interstitium). However, in 25% to 30% of cases, the radiological findings are atypical and unfamiliar to most radiologists, which cause difficulty for making a correct diagnosis. Many atypical forms of intrathoracic sarcoidosis have been described sporadically. We have collected cases with unusual radiological findings associated with pulmonary sarcoidosis (unilateral or asymmetric lymphadenopathy, necrosis or cavitation, large opacity, ground glass opacity, an airway abnormality and pleural involvement) and describe the typical forms of the disorder as well. The understanding of a wide range of the radiological manifestations of sarcoidosis will be very helpful for making a proper diagnosis.

Amiloidose ganglionar mediastinal em paciente com sarcoidose / Mediastinal lymph node amyloidosis in a patient with sarcoidosis

Paciente masculino, 27 anos, com sintomas respiratórios, linfonodomegalia cervical anterior bilateral e hepatomegalia. Os estudos de imagem evidenciaram linfonodomegalia hilar bilateral e infiltrado pulmonar. O paciente foi submetido a biópsias pulmonar e hepática, que evidenciaram presença de granulomas não caseosos. Também foi submetido à biópsia de linfonodo hilar, que revelou a presença de material amilóide. Os achados clínicos, radiológicos e histopatológicos foram compatíveis com sarcoidose e amiloidose ganglionar. A associação entre sarcoidose e amiloidose é raramente descrita.

A 27-year-old male patient presented with respiratory symptoms, bilateral enlargement of the cervical lymph nodes and enlarged liver. In the imaging studies, bilateral enlargement of the hilar nodes was observed, together with pulmonary infiltrate. The patient was submitted to lung and liver biopsies, which revealed noncaseating granulomas. The clinical, radiological and histopathological findings were consistent with sarcoidosis and lymph node amyloidosis. The combination of sarcoidosis and amyloidosis has rarely been reported.

Granulomatosis sarcoidea necrosante con compromiso sistémico / Necrotizing sarcoid granulomatosis with systemic involvement

A 70-year-old mapuche female presented with a 1 year history of weight loss, bilateral red painful eyes and corneal ulcer that evolved into perforation and uveal herniation with complete visual loss. Reddish and painful nodules appeared on the distal aspect of both lower extremities, that ulcerated after months. A thoracic CT scan showed multiple pulmonary nodules. Infectious diseases were ruled out. An open lung biopsy and a skin biopsy were performed and both showed non-caseating necrotizing granulomas and granulomatous arteritis. Steroids and cyclophosphamide were started with complete regression of skin and pulmonary lesions within a month. Corneal transplantation was done. After 6 months follow-up, the patient is on low-dose of steroids, free of disease with partial vision recovery.

Mujer mapuche de 70 años quien en el curso de 1 año presentó baja de peso, ojo rojo bilateral y úlcera corneal que evolucionó hacia la perforación con herniación uveal y pérdida de la visión. Posteriormente se agregaron lesiones nodulares, violáceas, sensibles, algunas ulceradas en las zonas distales de ambas extremidades inferiores. La TAC de tórax demostró múltiples nódulos pulmonares. Tras un estudio exhaustivo se descartaron la tuberculosis y otras infecciones. Tanto la biopsia de las lesiones cutáneas como la biopsia pulmonar obtenida mediante toracotomía confirmaron la presencia de granulomas necrotizantes no caseificantes y arteritis granulomatosa. Se trató con esteroides y ciclofosfamida con mejoría de su condición general y regresión de las lesiones cutáneas y pulmonares en menos de 1 mes. Se realizó un trasplante de cornea. A los seis meses de seguimiento continúa en tratamiento, no ha presentado recaídas y tiene recuperación parcial de la visión.

Sarcoidosis brocopulmonar: breve puesta al día y descripción de 8 casos / Bronchopulmonary sarcoidosis. Brief review and description of 8 cases

La sarcoidosis es una enfermedad de etiología desconocida, que afecta con mayor frecuencia a adultos jóvenes. El diagnóstico es clínico, radiológico e histopatológico y la presentación frecuente es la de síntomas constitucionales y respiratorios, acompañados de linfoadenopatías hiliares y mediastinales, con o sin compromiso del parénquima pulmonar. La confirmación es anatomopatológica con la demostración de granulomas no caseificantes en los tejidos afectados, con cultivos negativos para micobacterias y hongos. Presentamos los hallazgos clínicos, radiológicos e histopatológicos en 8 pacientes. Cuatro eran de sexo masculino y la edad promedio fue de 44 años (28-59). Dos de los pacientes se encontraban asintomáticos al momento del diagnóstico, cinco de ellos se presentaron con hallazgos toráxicos (tos, dolor retroesternal y arritmias) y uno con síntomas extratoráxicos (artritis de ambos tobillos). Todos presentaron adenopatías mediastinales en los estudios radiológicos y tomográficos y seis de ellos se encontraban en el estadio 2. En cuanto al tratamiento, dos pacientes remitieron espontáneamente, cuatro pacientes recibieron prednisona, uno requirió prednisona y azatioprina y de un paciente no contamos con registros de tratamiento. Uno de nuestros pacientes evolucionó desfavorablemente con aparición y recidiva de lesiones de eritema nodoso severas y bilaterales que motivaron la necesidad de tratamiento permanente con esteroides e inmunosupresores. Si bien se trata de una enfermedad de baja prevalencia en nuestro país, deberíamos mantener un alto índice de sospecha ante la presentación de síntomas respiratorios con lesiones parenquimatosas y adenopatías mediastinales, con o sin manifestaciones extratorácicas.

Sarcoidosis is a disease of unknown etiology affecting most frequently young adults. Diagnosis is based on clinical. Radiological and histopathological features and presentation is frequently of constitutional and respiratory symptoms, hilar and mediastinal adenopathies, with or without parenquimal involvement. Confirmation is histopathological with demonstration of non-caseificating granulomas in affected organs, with negative cultures for mycobacterium and fungi. We describe the clinical, radiological and histopatbological findings in 8 patients. Mean age was 44 years (28-59) and half the patients were male. Two patients were symptom-free at diagnosis, thoracic findings were present in five (cough, retroesternal pain and arrhytbmias) and one had extratboracic symptoms (ankle arthritis). All showed mediastinal adenopathies in radiological and tomographic images (six were in stage 2 and two in stage 1). 1/vo patients had spontaneous remission, four received oral steroids, one required oral steroids and azatbioprine and tbere was no treatment data on one patient. In one patient, recidiva of severe and bilateral erithema nodosum required long term treatment with steroids and immunosupressors. Although sarcoidosis is a low prevalent disease in our country, a high index of suspicion is advisable when facing patients with respiratory symptoms, parenquimal involvement and mediastinal adenopathies, with or without extrathoracic manifestations.

Circulating D-dimers as a marker of disease activity in pulmonary sarcoidosis.

BACKGROUND AND AIMS: The search is on to find an easily measurable marker of disease activity in sarcoidosis. The present study was carried out to evaluate the utility of plasma D-dimer as a marker of disease activity in sarcoidosis. METHODS: Thirty newly diagnosed cases of sarcoidosis with clinical indications for treatment and an equal number of matched healthy controls were studied for the presence of D-dimers (DD) in the plasma before starting treatment with oral prednisolone and after clinical remission. Semi-quantitative estimations of DD were done using the latex agglutination slide test method (Commercial Kit - Diagnostica Stago, France) as per the manufacturer's recommendations. RESULTS: The mean age of cases and controls were 45.43 +/- 8.5 (range 34-60) and 46.16 +/- 8.07 (range 32-61) years, respectively. Of the 30 patients, nine (30%) were DD positive at baseline. The DD positive patients presented more often with dyspnoea, had radiological stage III (7 out of 9) disease and abnormal spirometry compared to patients with no detectable DD in their plasma. Of the 16 patients re-evaluated after clinical remission, eight (50%) were D-dimer positive. Two of the five patients initially DD positive had become negative and five additional patients who were negative at baseline had become positive. CONCLUSIONS: Plasma D-dimers, which were positive in 30% of untreated patients of sarcoidosis, indicate patients with significant pulmonary parenchymal involvement; but have no correlation with clinical disease remission.

Sarcoidose gangliopulmonar: a propósito de dois casos / Ganglio-pulmonary sarcoidosis: apropos of 2 cases

Os autores relatam dois casos de sarcoidose com manifestaçoes intratorácicas envolvendo gânglios linfáticos e pulmoes (tipo radiológico II), além de comprometimento cutâneo peculiar em um dos pacientes. Abordam as bases clínicas para o seu reconhecimento e a importância dos exames complementares para o diagnóstico preciso desta doença multissistêmica, salientando os aspectos fundamentais de sua história natural, prognóstico e tratamento.