ABSTRACT
Na Medicina, como em muitas áreas da ocupação humana, o oculto tende a encantar. Talvez isso explique, em parte, o grande interesse em torno da sarcoidose, uma doença repleta de incógnitas e desafios ao seu entendimento. Esta revisão teve como objetivo apresentar os principais avanços no entendimento da imunopatogenia, diagnóstico e tratamento da sarcoidose pulmonar. Vários estudos têm enfatizado a importância do alelo DRB1*03 do antígeno leucocitário humano e da exposição ambiental na patogenia da doença. No tocante ao diagnóstico, o ultrassom endoscópico transesofágico, o ultrassom endobrônquico e a tomografia por emissão de pósitrons com 18F fluordesoxiglicose têm sido apresentados como exames promissores, inclusive na avaliação da resposta ao tratamento. Várias recomendações baseadas em evidências têm sugerido o uso de imunobiológicos nos casos de resistência aos corticosteroides, especialmente na sarcoidose refratária ao tratamento. O melhor entendimento da relação entre sarcoidose e exposição ambiental pode auxiliar na diferenciação dos vários fenótipos da doença. É possível que uma abordagem diagnóstica e terapêutica distinta possa ser utilizada em um futuro próximo, com base nesses fenótipos.
Subject(s)
Humans , Male , Female , Biological Therapy , Histocompatibility , Sarcoidosis, Pulmonary/diagnosis , Sarcoidosis, Pulmonary/epidemiology , Sarcoidosis, Pulmonary/immunology , Sarcoidosis, Pulmonary/therapy , Ultrasonography , Diagnostic Imaging , Lung Diseases, Interstitial , TherapeuticsABSTRACT
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.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Extracellular Matrix/immunology , Immunity, Cellular , Immunophenotyping/methods , Sarcoidosis/immunology , Analysis of Variance , Biopsy , Collagen/immunology , Elastic Tissue/immunology , Elastic Tissue/pathology , Extracellular Matrix/pathology , Granuloma, Respiratory Tract/immunology , Granuloma, Respiratory Tract/pathology , Lung/immunology , Lung/pathology , Lymph Nodes/immunology , Lymph Nodes/pathology , Lymphocytes/immunology , Macrophages, Alveolar/immunology , Sarcoidosis, Pulmonary/immunology , Sarcoidosis, Pulmonary/pathology , Sarcoidosis/pathologyABSTRACT
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.
Subject(s)
Humans , Female , Aged , Granuloma/diagnosis , Sarcoidosis, Pulmonary/diagnosis , Vasculitis/diagnosis , Skin Diseases/etiology , Granuloma/pathology , Necrosis , Radiography, Thoracic , Sarcoidosis, Pulmonary/immunology , Sarcoidosis, Pulmonary/pathology , Tomography, X-Ray Computed , Vasculitis/pathologyABSTRACT
BACKGROUND: The immune inflammatory process in patients with sarcoidosis is not only compartmentalized within the alveolar walls, but also involves the bronchial airways. Analysis of induced sputum has been used as a non-invasive tool for investigating the airways and may reflect the endobronchial and parenchymal inflammation in patients with sarcoidosis. This present study was designed to measure the soluble pro-inflammatory cytokine levels interleukin-1 (IL-1), interleukin-6 (IL-6), tumuor necrosis factor-alpha (TNF-alpha) and percentage of macrophages expressing these cytokines in induced sputum and bronchoalveolar lavage (BAL) fluid in patients with pulmonary sarcoidosis. METHODS: Sputum induction and BAL was carried out in 27 patients with newly diagnosed sarcoidosis. Control group consisted of six patients with a normal chest radiograph (three patients with carcinoma esophagus and three patients with doubtful history of hemoptysis). Induced sputum was also obtained from 10 non-smoking, non-atopic healthy controls. RESULTS: Percentage of macrophages expressing pro-inflammatory cytokines and soluble cytokine levels in induced sputum were higher in patients with sarcoidosis compared to both groups of controls. There was good correlation between IL-6 and TNF-alpha levels (r = 0.49, 0.58 p < 0.05) and percentage of macrophages expressing all three cytokines (r = 0.56-0.71, p < 0.01) between induced sputum and BAL fluid. Mild positive correlation between cytokine levels in sputum and age was also noted (r = 0.33-0.38, p < 0.05). CONCLUSIONS: Induced sputum may reflect changes in cytokine milieu in BAL in sarcoidosis.