Síndrome coronario agudo y enfermedad de Erdheim-Chester. Patogénesis e implicaciones terapéuticas

ResumenLa enfermedad de Erdheim-Chester es una histiocitosis celular diferente a la histiocitosis de Langerhans, de origen incierto. Se caracteriza por una implicación multi-orgánica debida a la infiltración de los histiocitos CD68+/CD1a-, en forma de xantogranulomas, que afectan principal y comúnmente a la metáfisis y diáfisis de huesos largos. El diagnóstico se realiza mediante biopsia, donde se revelan histiocitos CD68+/CD1a-, carencia de proteína S, y presencia de gránulos de Birbeck. Se ha subestimado la implicación cardiovascular. Reportamos un caso de un varón de 67 años con la enfermedad de Erdheim-Chester e infarto de miocardio agudo, debido a implicación coronaria, además de enfermedad ósea, vascular, pituitaria y retroperitoneal. Revisamos la literatura relevante y describimos el tratamiento clínico de estos pacientes.AbstractErdheim-Chester disease is a non-Langerhans cell histiocytosis of uncertain origin. It is characterized by multiorgan involvement due to infiltration of CD68+/CD1a- histiocytes, in the form of xantogranulomas, most commonly affecting the metaphysis and diaphysis of long bones. The diagnosis is made by biopsy showing CD68+/CD1ahistiocytes, lack of S protein and Birbeck granules. Cardiovascular involvement is underestimated. We report a case of a 67 year-old man with Erdheim-Chester disease and acute myocardial infarction due to coronary involvement, in addition to bone, vascular, pituitary and retroperitoneal disease. We review relevant literature and describe the clinical management of these patients

Reduced sTWEAK and Increased sCD163 Levels in HIVInfected Patients: Modulation by Antiretroviral Treatment, HIV Replication and HCV Co-Infection

Background: Patients infected with the human immunodeficiency virus (HIV) have an increased risk of cardiovascular disease due to increased inflammation and persistent immune activation. CD163 is a macrophage scavenger receptor that is involved in monocyte-macrophage activation in HIV-infected patients. CD163 interacts with TWEAK, a member of the TNF superfamily. Circulating levels of sTWEAK and sCD163 have been previously associated with cardiovascular disease, but no previous studies have fully analyzed their association with HIV. Objective: The aim of this study was to analyze circulating levels of sTWEAK and sCD163 as well as other known markers of inflammation (hsCRP, IL-6 and sTNFRII) and endothelial dysfunction (sVCAM-1 and ADMA) in 26 patients with HIV before and after 48 weeks of antiretroviral treatment (ART) and 23 healthy subjects. Results: Patients with HIV had reduced sTWEAK levels and increased sCD163, sVCAM-1, ADMA, hsCRP, IL-6 and sTNFRII plasma concentrations, as well as increased sCD163/sTWEAK ratio, compared with healthy subjects. Antiretroviral treatment significantly reduced the concentrations of sCD163, sVCAM-1, hsCRP and sTNFRII, although they remained elevated when compared with healthy subjects. Antiretroviral treatment had no effect on the concentrations of ADMA and sTWEAK, biomarkers associated with endothelial function. The use of protease inhibitors as part of antiretroviral therapy and the presence of HCV-HIV co-infection and/or active HIV replication attenuated the ART-mediated decrease in sCD163 plasma concentrations. Conclusion: HIV-infected patients showed a proatherogenic profile characterized by increased inflammatory, immuneactivation and endothelial-dysfunction biomarkers that partially improved after ART. HCV-HIV co-infection and/or active HIV replication enhanced immune activation despite ART.Redes Temáticas de Investigación en SIDA (ISCIII RETIC RD12/0017/0029 and RD12/0017/0037)Junta de Andalucía, Incentivos a proyectos de investigación de excelencia (CTS-6313, to Manolo Leal)Consejería de Salud (PI-0278)FIS PI10/00234 to LMBC and Programa Miguel Servet: CP10/00479 and PI13/00802 to JAMFundacion Lilly, FRIAT and ISCIII fund PI10/0007

Sobrecarga sentida por la figura del cuidador principal en una cohorte de pacientes pluripatológicos

ObjetivoConocer el perfil del cuidador principal (CP) y los factores relacionados con la sobrecarga sentida, en una cohorte multicéntrica de pacientes pluripatológicos (PP).DiseñoEstudio transversal, multicéntrico.EmplazamientoCuatro zonas básicas de salud del área sanitaria de los Hospitales Universitarios Virgen del Rocío, Sevilla.ParticipantesLa cohorte de PP se generó prospectivamente mediante el censado de todos los pacientes que cumplían los criterios de PP de la Consejería de Salud (2002): aquellos que tienen enfermedades crónicas de dos o más de las 7 categorías clínicas definidas.Mediciones principalesEl perfil del cuidador se determinó a todos los PP. El cansancio del CP se determinó mediante el índice de esfuerzo del cuidador (IEC). Los factores predictores se analizaron mediante los tests de la t de Student, ANOVA y Pearson.Posteriormente se realizó una regresión lineal multivariable paso a paso hacia delante.ResultadosAccedieron a la entrevista 461 (69% de los 662 elegibles) PP; 293 (63,6%) pacientes tenían CP, que en el 88% eran familiares de primer grado (146 [49,7%] de ellos, el cónyuge), de 62±15 años de edad, y el 80%, mujeres. El IEC fue > 7 puntos en el 41,5% y en general fue 5,35±3,5, mayor en los que cuidaban de PP con enfermedades neurológicas (7±3,2 frente a 4,5±3,3; p<0,0001). El IEC se correlacionó directamente con la vulnerabilidad clínica del PP (R=0,37; p<0,001), con el deterioro cognitivo por escala de Pfeiffer (R=0,4; p<0,0001), e inversamente con la situación funcional por índice de Barthel (R=−0,67; p<0,0001). La edad del paciente (p=0,03), su vulnerabilidad clínica (p=0,016) y el deterioro funcional (p<0,0001) y cognitivo (p=0,019) predijeron de forma independiente el IEC.ConclusionesEl perfil del CP de los PP se correspondió con mujeres familiares en primer grado de unos 60 años. Más de la tercera parte estaban sobrecargadas; los factores predictores fueron la edad, la vulnerabilidad clínica y el deterioro funcional y cognitivo del PP.ObjectiveTo determine the profile of the main caregiver (MC) and the factors associated with her/his care burden, in a multi-centre cohort of patients with multiple pathologies (PMP).DesignMulti-centre cross-sectional study.SettingFour health districts in the Virgen del Rocío University Hospitals Health Area, Seville, Spain.ParticipantsThe PMP cohort was created by checking all the patients who satisfied the health department criteria for PMP (2002): patients suffering from chronic diseases in 2 or more of the 7 clinical categories defined.Main measurementsThe profile of PMP caregiver was determined for all patients. The caregiver strain index (CSI) was determined by the index of care stress (ICS). Predictive factors were analysed by the Student t, ANOVA, and Pearson's tests. Multivariate analysis was performed by a forward stepwise linear regression model.ResultsThe interview was attended by 461 (69%) out of 662 eligible PMP. Of these, 293 (63.6%) had an MC whose mean age was 62 (15) years; 80% of them were women. First-degree relatives made up 88% of caregivers, with spouses 49.7% of them (n=146). In 41.5%, the CSI was >7points (mean CSI was 5.35 [3.5]). This was higher in those caring for PMP with neurological illnesses (7 [3.2 vs 4.5 [3.3]; P=.0001).The CSI was compared directly with the medical vulnerability of the PMP (R=0.37; P=.001), cognitive deterioration on the Pfeiffer scale (PS) (R=0.4; P=.0001), and inversely with functional status on Barthel's scale (BS) (R=-0.67; P=.0001). Patient's age (P=.03), his/her medical vulnerability (P=.016) and functional (P<.0001) and cognitive (P=.019) deterioration were independently associated with the CSI.ConclusionsThe profile of the MC of the PMP cohort corresponded mainly to first-degree female relatives around sixty years old. The burden of care was high in more than a third of them. Predictive factors were age, medical vulnerability, and the functional and cognitive deterioration of the PMP

Clinical characterization and outcomes of 85 patients with neurosarcoidosis

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confrmation of granulomatous disease was used to subclassify NS into defnite (confrmation in neurological tissue), probable (confrmation in extraneurological tissue) and possible (no histopathological confrmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulflled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classifcation proposed by Stern et al., 11 (13%) were classifed as a defnite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q= 0.018), a higher frequency of ocular (27% vs 10%, q< 0.001) and salivary gland (15% vs 4%, q= 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p= 0.02) in comparison with patients without NS. Neurosarcoidosis was identifed in 5.5% of patients. CNS involvement prevails signifcantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly diferentiated, and can be helpful not only in the early identifcation of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis

Cutaneous and Ganglion Sarcoidosis Induced by Polycaprolactone Facial Filler: A New Expression of ASIA Syndrome?

Dermal fillers are applied using a minimally invasive technique with a good safety profile. However, they can have side effects. We present the case of a patient who, 2 months after undergoing polycaprolactone (Ellansé®) injections, developed nodular facial and nodal lesions that were compatible with sarcoidosis on histology. This complication has not been previously described for polycaprolactone and could be the expression of an autoimmune syndrome induced by adjuvants

<i>Labra</i> de época romana en <i>Hispania</i>

Circular basins are very common functional and decorative elements in the Roman world, where they were referred to as <i>labra</i>. Rectangular basins have been often included within this category, but it is preferable to use the term <i>alvei</i> for them. Spanish historiography has not paid much attention to these elements, which is due more to a problem of publication than to an absence of these elements in the archaeological record. Sometimes, the terminological confusion has led to the identification of the fountains not by the architectural or sculptural elements from which the water spouted but by the space where they were placed. The historiography review and the reassessment of the archaeological records of the <i>labra</i> documented in the Iberian Peninsula, both in public and private spaces, has made it possible to analyze their origin, typology, function and material, as well as their archaeological context. Made of different varieties of both local and imported <i>marmora</i>, the fountain basins, in different sizes and morphologies, are usually linked to the roman baths to <i>atriums</i> and peristyles.<br><br>Los lavabos, pilas o tazas de fuente circulares son elementos funcionales y decorativos bastante comunes en el mundo romano donde recibían el nombre de <i>labra</i>. Dentro de esta categoría se han incluido a menudo también las tazas rectangulares, para las que se prefiere reservar el término <i>alvei</i>. En el ámbito de la antigua Hispania estos elementos han pasado bastante desapercibidos, lo que obedece a un problema de publicación más que de una ausencia en el registro arqueológico. En algunas ocasiones, la confusión terminológica ha llevado a identificar las fuentes no como el elemento arquitectónico o escultórico del que brotaba el agua, sino con el espacio físico donde se ubicó aquel. La revisión historiográfica de los <i>labra</i> documentados hasta el momento en la Península Ibérica, tanto en ámbitos públicos como privados, nos ha permitido analizar su procedencia, tipología, funcionalidad y material de fabricación, además de su contexto arqueológico. Fabricados en <i>marmora</i> de diferentes variedades, locales e importados, las tazas de fuente, que presentan diferentes tamaños y morfología, suelen estar vinculadas a edificios termales, así como a atrios y peristilos

Tocilizumab in refractory Caucasian Takayasu's arteritis: a multicenter study of 54 patients and literature review

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice. Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZMONO) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZCOMBO) was performed. Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZMONO and 31 (57.4%) on TCZCOMBO: MTX (n = 28), cyclosporine A (n = 2), azathioprine (n = 1). Patients on TCZCOMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal. Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin.Funding: This work was partially supported by RETICS Programs, RD08/0075 (RIER), RD12/0009/0013 and RD16/0012 from “Instituto de Salud Carlos III” (ISCIII) (Spain)