Enfermedad tiroidea autoinmune en pacientes colombianos con lupus eritematoso sistémico

Objetivos: Determinar la prevalencia y los factores asociados con el desarrollo de hipotiroidismo autoinmune (HA) en una cohorte de pacientes con lupus eritematoso sistémico (LES), y analizar la información actual en cuanto a la prevalencia e impacto de la enfermedad tiroidea autoinmune y la autoinmunidad tiroidea en pacientes con LES. Métodos: Este fue un estudio realizado en dos pasos. Primero, un total de 376 pacientes con LES fueron evaluados sistemáticamente por la presencia de: 1) HA confirmado, 2) positividad para anticuerpos tiroperoxidasa/tiroglobulina (TPOAb/TgAb) sin hipotiroidismo, 3) hipotiroidismo no autoinmune, y 4) pacientes con LES sin hipotiroidismo ni positividad para TPOAb/TgAb. Se construyeron modelos multivariados y árboles de regresión y clasificación para analizar los datos. Segundo, la información actual fue evaluada a través de una revisión sistemática de la literatura (RLS). Se siguieron las guías PRISMA para la búsqueda en las bases de datos PubMed, Scopus, SciELO y Librería Virtual en Salud. Resultados: En nuestra cohorte, la prevalencia de HA confirmado fue de 12% (Grupo 1). Sin embargo, la frecuencia de positividad para TPOAb y TgAb fue de 21% y 10%, respectivamente (Grupo 2). Los pacientes con LES sin HA, hipotiroidismo no autoinmune ni positividad para TPOAb/TgAb constituyeron el 40% de la corhorte. Los pacientes con HA confirmada fueron estadísticamente significativo de mayor edad y tuvieron un inicio tardío de la enfermedad. El tabaquismo (ORA 6.93, IC 95% 1.98-28.54, p= 0.004), la presencia de Síndrome de Sjögren (SS) (ORA 23.2, IC 95% 1.89-359.53, p= 0.015) y la positividad para anticuerpos anti-péptido cíclico citrulinado (anti-CCP) (ORA 10.35, IC 95% 1.04-121.26, p= 0.047) se asociaron con la coexistencia de LES-HA, ajustado por género y duración de la enfermedad. El tabaquismo y el SS fueron confirmados como factores predictivos para LES-HA (AUC del modelo CART = 0.72). En la RSL, la prevalencia de ETA en LES varío entre 1% al 60%. Los factores asociados con esta poliautoinmunidad fueron el género femenino, edad avanzada, tabaquismo, positividad para algunos anticuerpos, SS y el compromiso articular y cutáneo. Conclusiones: La ETA es frecuente en pacientes con LES, y no afecta la severidad del LES. Los factores de riesgo identificados ayudarán a los clínicos en la búsqueda de ETA. Nuestros resultados deben estimular políticas para la suspensión del tabaquismo en pacientes con LES.

El costo de la atención ambulatoria del lupus eritematoso sistémico en Colombia. Contrastes y comparaciones con otras poblaciones.

Introducción: el lupus eritematoso sistémico (LES) es considerado una enfermedad de alto costo. La expresión clínica de la enfermedad depende de la ubicación geografía y la etnicidad. El objetivo de este estudio fue el calcular los costos ambulatorios relacionado al LES en una cohorte colombiana, identificar los predictores de costos y comparar nuestro resultados con otras poblaciones. Métodos: Se realizó una aproximación de tipo prevalencia en 100 pacientes LES en quienes se evaluaron los costos directos médicos, directos no médicos, indirectos e intangibles. Todos los costos médicos fueron evaluados usando una metodología abajo hacia arriba. Los costos directos fueron valorados desde una perspectiva social usando una metodología de micro-costeo. Los costos indirectos se evaluaron mediante una aproximación de capital humano, y los costos intangibles calculados a partir de los años de vida ajustados por calidad (AVAC). Se analizaron los datos por medio de un análisis multivariado. Para comparaciones con otras poblaciones todos los costos fueron expresados como la razón entre los costos y producto interno bruto nacional per cápita. Resultados: La media de costos totales fue 13.031±9.215 USD (ajustados por el factor de conversión de paridad del poder adquisitivo), lo cual representa el 1,66 del PIB per capita de Colombia. Los costos directos son el 64% de los costos totales. Los costos médicos representan el 80% de los costos directos,. Los costos indirectos fueron el 10% y los costos intangibles el 25% de los costos totales. Los medicamentos representaron el 45% de los costos directos. Mayores costos se relacionaron con el estrato socioeconómico, seguro médico privado, AVAC, alopecia, micofenolato mofetilo, y terapia anticoagulante. Los costos directos ajustados de los pacientes con LES en Colombia fueron mayores que en Norte América y en Europa. Conclusiones: el LES impone una carga económica importante para la sociedad. Los costos relacionados con la atención médica y AVAC fueron los principales contribuyentes al alto costo de la enfermedad. Estos resultados pueden ser referencia para determinar políticas en salud pública así como comparar el gasto en salud de forma internacional.

Factores asociados a mortalidad en pacientes colombianos con enfermedades autoinmunes en la unidad de cuidado intensivo, de un hospital de tercer nivel en Bogotá Colombia

Antecedentes: El interés en las enfermedades autoinmunes (EA) y su desenlace en la unidad de cuidado intensivo (UCI) han incrementado debido al reto clínico que suponen para el diagnóstico y manejo, debido a que la mortalidad en UCI fluctúa entre el 17 – 55 %. El siguiente trabajo representa la experiencia de un año de nuestro grupo en un hospital de tercer nivel. Objetivo: Identificar factores asociados a mortalidad particulares de los pacientes con enfermedades autoinmunes que ingresan a una UCI, de un hospital de tercer nivel en Bogotá, Colombia. Métodos: El uso de análisis de componentes principales basado en el método descriptivo multivariado y análisis de múltiple correspondencia fue realizado para agrupar varias variables relacionadas con asociación significativa y contexto clínico común. Resultados: Cincuenta pacientes adultos con EA con una edad promedio de 46,7 ± 17,55 años fueron evaluados. Los dos diagnósticos más comunes fueron lupus eritematoso sistémico y esclerosis sistémica, con una frecuencia de 45% y 20% de los pacientes respectivamente. La principal causa de admisión en la UCI fue la infección seguido de actividad aguda de la EA, 36% y 24% respectivamente. La mortalidad durante la estancia en UCI fue del 24%. El tiempo de hospitalización antes de la admisión a la UCI, el choque, soporte vasopresor, ventilación mecánica, sepsis abdominal, Glasgow bajo y plasmaféresis fueron factores asociados con mortalidad. Dos fenotipos de variables fueron definidos relacionadas con tiempo en la UCI y medidas de soporte en UCI, las cuales fueron asociadas supervivencia y mortalidad. Conclusiones: La identificación de factores individuales y grupos de factores por medio del análisis de componentes principales permitirá la implementación de medidas terapéutica de manera temprana y agresiva en pacientes con EA en la UCI para evitar desenlaces fatales.

Effect of heparin and fractionated heparin on trophoblast invasion

BACKGROUND: Heparin can significantly reduce pregnancy complications in women with certain thrombophilias, such as antiphospholipid syndrome. Recent reports suggest that heparin may act by mechanisms other than anticoagulation. However, the effect of heparin on trophoblast biology in the absence of thrombophilia has not been extensively investigated. Therefore, this study aimed to evaluate trophoblast invasion, using an established cell line and primary extravillous trophoblasts (EVTs), following exposure to heparin and fractionated heparin. METHODS: An EVT cell line (SGHPL-4) was used to study invasion in the presence of hepatocyte growth factor (HGF) and varying concentrations of fractionated and unfractionated heparin. These experiments were repeated using first trimester primary EVTs. RESULTS: Both forms of heparin significantly reduced HGF-induced invasion in the SGHPL-4 cell line. This suppression of invasion appeared to be dose-dependent for fractionated heparin. In primary EVT cells, fractionated heparin also demonstrated significant suppression of invasion. CONCLUSIONS: Heparin has the potential to reduce trophoblast invasion in cell lines and first trimester EVT cells. This article highlights the need for further evaluation of these medications in vitro and in vivo, especially when used in the absence of thrombophilic disorders.

Apresentação pediátrica da síndrome antifosfolípide

OBJETIVO: Descrever as características clínicas, laboratoriais e de desfecho de uma série de casos com diagnóstico definido de síndrome antifosfolípide (SAF) pediátrica. MÉTODOS: Estudo observacional-retrospectivo de referência pediátrica terciária, que identificou os casos por meio de evento vascular, trombose venosa ou oclusão arterial, determinação de anticorpos anticardiolipina (IgG e IgM) e teste do anticoagulante lúpico. RESULTADOS: Foram identificados cinco casos atendidos nos últimos cinco anos, sendo dois meninos e três meninas. A trombose venosa ocorreu em seios venosos cerebrais (2), fibular (2), poplítea (1), femoral (1), intestinal (1), renal (1), acompanhados por oclusão arterial intestinal (1), de artéria renal (1) e artéria digital (1), esta resultando gangrena periférica como evento recorrente durante anticoagulação com warfarina. Um abortamento espontâneo ocorreu em uma adolescente em vigência de púrpura trombocitopênica, evoluindo com anemia hemolítica (síndrome de Evans) e desfecho fatal por hemorragia. A investigação laboratorial em todos os casos resultou, pelo menos, uma determinação positiva de anticardiolipina IgG e/ou IgM, sendo considerados como SAF primária. Três dos casos estão em seguimento com anticoagulação oral. CONLUSÃO: A trombose venosa cerebral e de extremidades foram os eventos mais freqüentes. A presente série alerta para a investigação e o diagnóstico precoces, com abordagem multidisciplinar para o tratamento.

Síndrome antifosfolípide e trombocitopenia na infância

Objective: To report the case of a child diagnosed with antiphospholipid syndrome associated with severe thrombocytopenia, and to review the literature on the subject. Case description: Child aged nine years and eight months old with severe thrombocytopenia associated with a positive anticardiolipin antibody. Data were collected by clinical history, physical examination, and laboratorial exams. Diagnosis was confirmed according to criteria established for the antiophospholipid syndrome, associated with the presence of the most common manifestations of the syndrome in children: livedo reticularis and thrombocytopenia. Comments: The antiphospholipid syndrome is an uncommon pediatric disease, and clinical manifestations such as decreased platelet number should be considered.

Trombofilias e abortos recorrentes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-term clinical and ultrasonographic evaluation of thrombophilic patients with deep venous thrombosis

OBJECTIVE:The purpose of this study was to evaluate the long term clinical and ultrasonographic outcomes of thrombophilic patients with deep venous thrombosis (DVT).METHOD:Cohort study, retrospective case-control with cross-sectional analysis. Thirty-nine thrombophilic patients and 25 non-thrombophilic patients were assessed 76.3 ± 45.8 months after diagnosis. Demographic and family data were collected, as well as data from clinical and therapeutic progress, and physical and ultrasound examinations of the limbs were performed. Groups were matched for age and gender and the variables studied were compared across groups.RESULTS:Deep venous thrombosis was more frequent in women. The most common thrombophilias were antiphospholipid syndrome and factor V Leiden mutation. There was no difference between groups in terms of the number of pregnancies or miscarriages and the majority of women did not become pregnant after DVT. Non-spontaneous DVT prevailed. Proximal DVT and DVT of the left lower limb were more frequent, and the main risk factor was use of oral contraceptives. All patients were treated with anticoagulation. There was a higher frequency of pulmonary embolism in non-thrombophilic patients. Most patients considered themselves to have a normal life after DVT and reported wearing elastic stockings over at least 2 years. Seventy-one percent of patients had CEAP > 3, with no difference between groups. Deep venous reflux was more frequent in thrombophilic patients.CONCLUSION:There were no significant differences between groups with respect to most of the variables studied, except for a higher frequency of pulmonary embolism in non-thrombophilic patients and greater frequency of deep venous reflux in thrombophilic patients.

Autoimmune disease and multiple autoantibodies in 42 patients with RASopathies

The association of RASopathies [Noonan syndrome (NS) and Noonan-related syndromes] and autoimmune disorders has been reported sporadically. However, a concomitant evaluation of autoimmune diseases and an assessment of multiple autoantibodies in a large population of patients with molecularly confirmed RASopathy have not been performed. The clinical and laboratory features were analyzed in 42 RASopathy patients, the majority of whom had NS and five individuals had Noonan-related disorders. The following autoantibodies were measured: Anti-nuclear antibodies, anti-double stranded DNA, anti-SS-A/Ro, anti-SS-B/La, anti-Sm, anti-RNP, anti-Scl-70, anti-Jo-1, anti-ribosomal P, IgG and IgM anticardiolipin (aCL), thyroid, anti-smooth muscle, anti-endomysial (AE), anti-liver cytosolic protein type 1 (LC1), anti-parietal cell (APC), anti-mitochondrial (AM) antibodies, anti-liver-kidney microsome type 1 antibodies (LKM-1), and lupus anticoagulant. Six patients (14%) fulfilled the clinical criteria for autoimmune diseases [systemic lupus erythematous, polyendocrinopathy (autoimmune thyroiditis and celiac disease), primary antiphospholipid syndrome (PAPS), autoimmune hepatitis, vitiligo, and autoimmune thyroiditis]. Autoimmune antibodies were observed in 52% of the patients. Remarkably, three (7%) of the patients had specific gastrointestinal and liver autoantibodies without clinical findings. Autoimmune diseases and autoantibodies were frequently present in patients with RASopathies. Until a final conclusion of the real incidence of autoimmunity in Rasopathy is drawn, the physicians should be alerted to the possibility of this association and the need for a fast diagnosis, proper referral to a specialist and ultimately, adequate treatment. (c) 2012 Wiley Periodicals, Inc.

Chronic mucocutaneous candidiasis and systemic lupus erythematosus: a new variant of chronic mucocutaneous candidiasis?

Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to Candida infection of skin, nails, and mucous membranes. Autoimmune endocrinopathies are common in CMC patients, but there are no reports of the involvement of systemic autoimmune disorders. We present here the first case of this kind of association in a patient with an autosomal dominant variant of CMC. The individual had had this disorder since childhood and systemic lupus erythematosus with secondary antiphospholipid syndrome, as well as renal, articular and hepatic manifestations without thymoma.

Síndrome antifosfolípide e dermatomiosite/polimiosite: uma rara associação

A associação entre a síndrome antifosfolípide e as miopatias inflamatórias idiopáticas tem sido raramente descrita na literatura. No presente trabalho relatamos dois pacientes com síndrome antifosfolípide diagnosticados com dermatomiosite ou polimiosite. Realizamos também uma revisão da literatura acerca dessa sobreposição de duas entidades autoimunes sistêmicas.

Trombose coronariana como primeira complicação da aíndrome antifosfolípide

A síndrome do anticorpo antifosfolípide (SAF) é uma trombofilia autoimune, caracterizada pela presença de anticorpos plasmáticos contra fosfolípides, associada a episódios recorrentes de trombose venosa e/ou arterial e morbidade gestacional (especialmente abortamento de repetição). Reportamos o caso de uma paciente feminina, jovem, com diagnóstico de lúpus eritematoso sistêmico (LES), associado à presença de anticorpos antifosfolípide de longa data, com apresentação de infarto agudo do miocárdio (IAM) por trombose proximal da artéria descendente anterior como primeira complicação clínica da SAF.

Síndrome antifosfolípide e dermatomiosite/polimiosite: uma rara associação

A associação entre a síndrome antifosfolípide e as miopatias inflamatórias idiopáticas tem sido raramente descrita na literatura. No presente trabalho relatamos dois pacientes com síndrome antifosfolípide diagnosticados com dermatomiosite ou polimiosite. Realizamos também uma revisão da literatura acerca dessa sobreposição de duas entidades autoimunes sistêmicas.

Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

[Coumarin-induced necrotic purpura of the skin -- case report and review of the literature]

We report the case of a 28-year old woman with extensive red-black colored lesions of the skin on the left thigh, which appeared without trauma. The disease arrived during longterm coumarin therapy because of a deep vein thrombosis and an antiphospholipid syndrome. After consideration of the differential diagnoses and due to the typical clinical picture we made the diagnosis of coumarin necrosis. We review the clinical and therapeutic features for this rare complication.