Esclerosis sistémica sin esclerodermia, un desafío diagnóstico para el clínico: caso clínico y revisión de la literatura / Systemic sclerosis sine scleroderma: a clinical diagnostic challenge: clinical case and literature review

La Esclerodermia es una patología poco frecuente que afecta principalmente la piel, de ahí su nombre. Desde ese punto de vista existen diferentes clasificaciones siendo las más frecuentes: forma Difusa y Limitada. Existe también otra forma de presenta-ción, muy infrecuente y difícil de identificar: la esclerosis sistémica sin esclerodermia (eSSe). En este reporte presentamos el caso de una paciente de 50 años, que cursa con injuria renal aguda de origen inexplicado con algunos elementos de laboratorio de microangiopatía trombótica, sin clínica sugerente de esclerosis sistémica progre-siva y con laboratorio inicial difícil, lo que retrasó el diagnóstico y por ende el trata-miento. En este caso se obtiene el diagnóstico de crisis renal esclerodérmica, por los hallazgos compatibles de microangiopatía trombótica arrojados por la biopsia renal.

Systemic sclerosis is a rare connective tissue disease that is characterized by thickening of the skin (scleroderma). The disease has 2 main presentations forms: diffuse and limited. However, it can also manifest without scleroderma, known as systemic sclerosis sine scleroderma (ssSSc). In this report, we describe the case of a 50 years female who debut with acute renal injury and possible microangiopathy thrombotic elements in laboratory findings, in absence of signs of scleroderma at physical examination or initial laboratory test results, causing the delay of accurate diagnosis and management. Renal biopsy findings were compatible with thrombotic microangiopathy and renal sclerodermic crisis, which guided the diagnosis and subsequent management.

Enfermedad pulmonar difusa en esclerodermia: diagnóstico y tratamiento / Intetstitial lung disease in scleroderma: diagnosis and treatment

Scleroderma is among the connective tissue diseases (CTD) with more pulmonary involvement. More than half of scleroderma patients have some kind of interstitial lung disease (ILD), and this is currently the leading cause of death due to the disease itself. The main risk factor for ILD is the autoantibodie profile, and the period of greatest risk of developing ILD is among the first 3-5 years of disease. The most common histopathological form is NSIP, but the histopathological subtype has no influence on prognosis or response to treatment. Given the fact that some ILD patients will remain stable and because of the lack of a really effective and risk free treatment, immunosuppressive therapy is generally reserved for patients with extensive and / or progressive disease. The main risk factors for progressive disease are pulmonary extent and functional impairment. With currently available therapies the more realistic goal is stabilization of lung disease. The most widely used immunosuppressive induction therapy is Cyclophosphamide (CYC), but there is enough evidence to support the use of Mycophenolate Mofetil (MMF). As maintenance therapy, options are MMF and Azathioprine. Periodic clinical and functional reassessment is of vital importance, to monitor functional progression and/or the response to immunosuppressive therapy...

La esclerodermia está entre las enfermedades del tejido conectivo (ETC) que con mayor frecuencia presentan enfermedad pulmonar difusa (EPD), y se encuentra en más de la mitad de los pacientes. Actualmente la EPD representa la principal causa de muerte atribuible a la propia enfermedad. El principal factor de riesgo es el perfil de autoanticuerpos, y el período de mayor riesgo de desarrollar EPD son los primeros tres a cinco años de enfermedad. La forma histopatológica más frecuente es neumonía intersticial no específica (NINE), pero el subtipo histopatológico no tiene mayor influencia en el pronóstico ni en la respuesta al tratamiento. Dada la existencia de pacientes con EPD intrínsecamente estable y a la ausencia de una terapia realmente efectiva y exenta de riesgos, la inmunosupresión se reserva en general para pacientes con enfermedad extensa y/o progresiva. Lo parámetros que mejor se han correlacionado con el riesgo de progresión son la extensión radiológica y el compromiso de la función pulmonar. Con las terapias actualmente disponibles, el objetivo más realista es la estabilización del compromiso pulmonar. El Inmunosupresor más utilizado para la terapia de inducción es ciclofosfamida (CYC), pero existe evidencia suficiente que avala el uso de micofenolato mofetil (MMF). Como terapia de mantención las principales opciones son azatioprina y MMF. La reevaluación clínica y funcional periódica es fundamental, para monitorizar la progresión y/o la respuesta al tratamiento inmunosupresor...

Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis / Avaliacao imuno-histoquimica e morfometrica de COX-1 e COX-2 no remodelamento pulmonar na fibrose pulmonar idiopatica e na esclerose sistemica

OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc) and idiopathic pulmonary fibrosis (IPF) patients, correlating that expression with patient survival. METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP) in SSc patients and usual interstitial pneumonia (UIP) in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival. RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP), and low COX-1 expression in alveolar septa. CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that. .

OBJETIVO: Estudar a expressão de COX-1 e COX-2 em áreas pulmonares remodeladas em pacientes com esclerose sistêmica (ES) ou fibrose pulmonar idiopática (FPI) e correlacioná-la com a sobrevida desses pacientes. MÉTODOS: Examinamos espécimes de biópsia pulmonar a céu aberto de 24 pacientes com ES e de 30 pacientes com FPI, utilizando-se tecido pulmonar normal como controle. Os padrões histológicos incluíram pneumonia intersticial não específica (PINE) fibrótica em pacientes com ES e pneumonia intersticial usual (PIU) nos pacientes com FPI. Imuno-histoquímica e histomorfometria foram usadas para avaliar a expressão celular de COX-1 e COX-2 em septos alveolares, vasos e bronquíolos, sua correlação com provas de função pulmonar e seu impacto na sobrevida. RESULTADOS: A expressão de COX-1 e COX-2 em septos alveolares foi significativamente maior em FPI-PIU e ES-PINE do que no tecido controle. Não houve diferença entre FPI-PIU e ES-PINE quanto à expressão de COX-1 e COX-2. A análise multivariada baseada no modelo de regressão de Cox mostrou que os fatores associados a baixo risco de morte foram ter idade menor, valores elevados de DLCO/volume alveolar, FPI, e alta expressão de COX-1 em septos alveolares, ao passo que os fatores associados a alto risco de morte foram ter idade maior, valores baixos de DLCO/volume alveolar, ES (com PINE) e baixa expressão de COX-1 em septos alveolares. CONCLUSÕES: Nossos resultados sugerem que estratégias de prevenção de baixa síntese de COX-1 terão maior impacto sobre a ES, ao passo que as de prevenção de alta síntese de COX-2 terão maior impacto sobre a FPI. Porém, são necessários ensaios clínicos randomizados prospectivos para confirmar essa hipótese. .

Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Esclerodermia mortal / Fatal scleroderma

Se presentan dos casos de esclerodermia con restricción pulmonar grave: un paciente masculino de 23 años con fiebre de 20 días de evolución asociada a disnea de medianos esfuerzos y enfermedad de Raynaud; y una paciente de 31 años con disnea de medianos esfuerzos y enfermedad de Raynaud. Ambos fallecieron por insuficiencia respiratoria aguda. La trascendencia de mostrar estos dos casos radica en la súbita presentación de la insuficiencia respiratoria en esclerodermia de reciente inicio

Ecocardiografia na esclerose sistêmica progressiva / Echocardiography in sistemic progressive sclerosis

Estudo ecocardiografico foi conduzido em 23 pacientes portadores de esclerose sistêmica progressiva(ESP),encontrando-se 13 casos com anormalidades:tres de calcificaçao de valvula aórtica,um de disfunçao de ventriculo esquerdo,tres de hipertensao arterial pulmonar,dois de miocardiopatia dilatada e quatro de pequeno derrame pericardio.O acometimento cardiaco na ESP representa 15 por cento das causas de morte,embora produzam poucos sintomas clinicos nas fases iniciais da doença.Os autores concluem que o ecocardiograma deve ser incluido entre os procedimentos de rotina para a avaliaçao dos casos de ESP.