Genética de la artritis reumatoide en Chile / Genetics of rheumatoid arthritis in Chile

La artritis reumatoide (AR) es una enfermedad sistémica crónica y autoinmune, que afecta principalmente a las articulaciones sinoviales. Al igual que ocurre con muchas enfermedades autoinmunes, la etiología de la AR es multifactorial y desconocida. La susceptibilidad genética es evidente en AR, situando su heredabilidad en aproxima-damente el 60%. La importancia del conocimiento de los factores genéticos asociados con la AR se sitúa en la contribución a la comprensión de los mecanismos patogénicos de la enfermedad, así como a su aplicación clínica que nos acerque a un tratamiento más personalizado de los pacientes por medio de marcadores de riesgo, diagnóstico y/o pronóstico. En este artículo se revisan los factores genéticos de la AR, y se hace una aproximación a la situación en poblaciones latinoamericanas en general, y chile-na en particular.

Rheumatoid arthritis (RA) is an autoimmune inflammatory rheumatic disease that affects many tissues and organs, mainly synovial joints. Like many autoimmune dis-eases, the etiology of RA is multifactorial and unknown. Genetic susceptibility is evi-dent in RA, with its heritability around the 60%.The relevance of the knowledge of the genetic factors associated with RA relies on its contribution to the understanding of the pathological mechanisms of the disease, and the clinical applicability. This better understanding let us develop a more personalized treatment through genetic markers for risk, diagnostic and prognostic. In this paper, genetic factors of RA are reviewed and a general view of the Latin American populations, and particularly Chilean, is made.

Un caso inusual de quiste sebáceo infectado por Dermabacter hominis / Unusually infected sebaceous cyst by Dermabacter hominis

La especie Dermabacter hominis está constituida por bacilos gram positivos corineformes, anaerobios facultativos, que forman parte de la microbiota residente de la piel. Excepcionalmente se ha asociado a estos microorganismos con infecciones en pacientes inmunocomprometidos o muy debilitados. Se describe el caso de una mujer adulta joven, inmunocompetente, con un quiste sebáceo en el cuello, infectado por D. hominis como único agente etiológico. Se logró la identificación fenotípica del agente causal mediante pruebas simples basadas en el esquema originalmente propuesto por Funke y Bernard, factibles de ser realizadas en un laboratorio hospitalario de microbiología. Características fenotípicas como la morfología cocoide, el olor acre/espermático, la hidrólisis de la esculina, la producción de pirrolidonil arilamidasa y de lisina y ornitina descarboxilasas son pruebas claves en la identificación de D. hominis. La espectrometría de masas (MALDI-TOF MS) confirmó la identificación fenotípica.

Dermabacter hominis species is constituted by Gram positive facultative anaerobic coryneform rods being part of the resident microbiota human skin, and exceptionally associated to infections in immunocompromised or severely debilitated patients. An immunocompetent young adult woman with a neck sebaceous cyst infected by D. hominis as unique etiologic agent is presented. Phenotypic identification of the causative agent was achieved through simple tests, based on the originally scheme proposed by Funke and Bernard, and feasible to be performed in a hospital Microbiology Laboratory. Phenotypic characteristics as coccoid morphology, the acrid/spermatic odor, esculin hydrolysis, the production of pyrrolidonyl-arylamidase, lysine and ornithine decarboxylase, are key tests to identify D. hominis. The matrix-asisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the phenotypic identification.

[Unusually infected sebaceous cyst by Dermabacter hominis]. / Un caso inusual de quiste sebáceo infectado por Dermabacter hominis.

Dermabacter hominis species is constituted by Gram positive facultative anaerobic coryneform rods being part of the resident microbiota human skin, and exceptionally associated to infections in immunocompromised or severely debilitated patients. An immunocompetent young adult woman with a neck sebaceous cyst infected by D. hominis as unique etiologic agent is presented. Phenotypic identification of the causative agent was achieved through simple tests, based on the originally scheme proposed by Funke and Bernard, and feasible to be performed in a hospital Microbiology Laboratory. Phenotypic characteristics as coccoid morphology, the acrid/spermatic odor, esculin hydrolysis, the production of pyrrolidonyl-arylamidase, lysine and ornithine decarboxylase, are key tests to identify D. hominis. The matrix-asisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the phenotypic identification.

Genética, HLA-B27 y espondilitis anquilosante: 40 años / Genetics of ankylosing spondylitis

Ankylosing spondylitis (AS) is a prototypical inflammatory disease of the locomotor system affecting axial skeleton. It is part of the general group of spondyloarthopathies (SpA). Its strong association with histocompatibility antigen HLA-B27 is known since 1973. However, HLA-B27 contribution to AS genetic risk is approximately 16%. Therefore, other genes are necessarily involved in the pathogenesis of the disease. Genomic development and the possibility of making genome wide screening have contributed enormously to the study of the disease. In this paper, we describe the actual knowledge about AS genetic risk, which has contributed to understand the influence of HLA-B27 on the etiology and pathogenesis of the disease. We also intend to foresee how these findings will result in an improvement of patients’ quality of life.

Nuevas estrategias en el tratamiento del síndrome antifosfolípido / New alternatives for the treatment of antiphospholipid syndrome. A literature review

For years the mainstay of antiphospholipid syndrome treatment has been anticoagulation and antiplatelet therapy, but the autoimmune nature of the disease, and complications of these therapies, created the need to develop new therapeutic strategies. New therapeutic alternatives inhibit at different levels, the cascade of events leading to the pro-thrombotic state characteristic of the antiphospholipid syndrome. We conducted a literature review of these new treatments, focusing on the pathophysiological bases that support them and their possible clinical applications.

Clinical and genetic features of hereditary periodic fever syndromes in Hispanic patients: the Chilean experience.

Hereditary periodic fever syndromes (HPFS) are rare genetic diseases characterized by recurrent episodes of inflammation. Little information is available concerning HPFS in Latin American Hispanic population. The purpose of this study was to determine the clinical and genetic features of HPFS in Chilean population. A multicenter retrospective study of Hispanic Chilean patients with genetically confirmed HPFS was performed. We included 13 patients, 8 with familial Mediterranean fever (FMF) and 5 with TNF receptor-associated periodic syndrome (TRAPS), evaluated at rheumatology or pediatric rheumatology clinics between January 2007 and December 2010. Median age of symptoms onset was 8 years (range 1-35) and 8 years (range 0.3-21) for FMF and TRAPS, respectively. Median duration of fever was 3 days (range 2.5-15) for FMF and 21 days (range 9.5-30) for TRAPS. Genotyping of the MEFV gene in FMF patients revealed a homozygous M694V missense mutation in one patient, and heterozygous missense mutations in seven patients: M694V (n = 3), E148Q, R717H, A744S, and A511V. Sequencing of the TNFRSF1A gene in TRAPS patients revealed heterozygous missense mutations in four patients: T50M, C30R, R92Q, and IVS3+30:G→A, and a two-base pair deletion (IVS2-17_18del2bpCT) in one patient. Mutation in MEFV R717H and mutations in TNFRSF1A IVS2-17_18del2bpCT and IVS3+30:G→A are novel and have not been described previously. This study reports the largest series of genetically confirmed HPFS in Latin America, and adds evidence regarding the clinical and genetic characteristics of patients with FMF and TRAPS in Hispanic population. Mutations identified in MEFV and TNFRSF1A genes include defects reported in other ethnicities and novel mutations.

Differential features between primary ankylosing spondylitis and spondylitis associated with psoriasis and inflammatory bowel disease.

OBJECTIVE: To describe differential characteristics of axial involvement in ankylosing spondylitis (AS) as compared with that seen in psoriatic arthritis (PsA) and inflammatory bowel disease (IBD) in a cohort of Ibero-American patients. METHODS: This study included 2044 consecutive patients with spondyloarthritis (SpA; ESSG criteria). Demographic, clinical, disease activity, functional ability, quality of life, work status, radiologic, and therapeutic data were evaluated and collected by RESPONDIA members from different Ibero-American countries between June and December 2006. Patients selected for analysis met modified New York criteria (mNY) for AS. RESULTS: A total of 1264 patients met the New York criteria for AS: 1072 had primary AS, 147 had psoriatic, and 45 had IBD-associated spondylitis. Median disease duration was comparable among the 3 patient groups. Patients with primary AS were significantly younger (p = 0.01) and presented a higher frequency of males (p = 0.01) than the other 2 groups. Axial manifestations such as inflammatory back pain and sacroiliac pain were significantly more frequent in patients with primary AS (p = 0.05) versus other groups, whereas frequency of dactylitis, enthesitis, and peripheral arthritis was more common in patients with psoriatic spondylitis (p = 0.05). Spinal mobility was significantly more limited in patients with primary AS versus the other 2 groups (p = 0.0001). Radiologic changes according to BASRI total score were equally significant in primary AS. Disease activity (BASDAI), functional ability (BASFI), and quality of life (ASQoL) scores were comparable in the 3 groups. CONCLUSION: Patients with primary AS had more severe axial involvement than those with spondylitis associated with psoriasis or IBD. Functional capacity, disease activity, and quality of life were comparable among the groups studied.

Peritonitis en diálisis peritoneal: análisis comparativo de los índices de seguimiento en dos períodos consecutivos en un hospital universitario: [revisión] / Peritonitis in peritoneal dialysis: comparative analysis of the follow-up indexes in two consecutive periods in a university hospital: [review]

La peritonitis (P) ha sido la complicación más importante de la diálisis peritoneal crónica (DPC) y la causa más frecuente de exclusión del programa. En este trabajo se evaluaron los índices de seguimiento de las P en DPC en 2 períodos consecutivos de 10 años en un hospital universitario, tras los avances de la técnica dialítica y la aplicación de un programa de educación médica continua y de los pacientes.

[Pseudotumor cerebri secondary to Behçet disease. Report of one case]. / Pseudotumor cerebri como una manifestación excepcional de la enfermedad de Behçet. Caso clínico.

The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59% of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. She gave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, a glucose concentration of 64 mg/dl, 20 fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was also found. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

Pseudotumor cerebri como una manifestación excepcional de la enfermedad de Behçet: caso clínico / Pseudotumor cerebri secondary to Behçet disease: report of one case

The classical manifestations of Behçet disease are mouth ana genital ulcers, cutaneous lesions ana ocular involvement. The central nervous system is affected in 5 to 59 percent of the cases, usually in the form of meningoencephalitis or sinus venous thrombosis. We report a 17-year-old femóle presenting with a two weeks history of progressive headache, nausea and blurred vision. An initial magnetic resonance was normal. Fifteen days later she was admitted to the hospital due to progression of visual impairment. Shegave a history of oral ulcers and arthralgias. A new magnetic resonance was normal. A lumbar puncture showed a cerebrospinal fluid with a protein concentration of 14 mg/dl, aglucose concentration of 64 mg/dl, 20fresh red blood cells and a pressure of 26 cm H(2)0. The diagnosis of a pseudotumor cerebri, secondary to Behçet disease was raised and the patient was treated with colchicine and acetazolamide. The evolution was torpid and an anterior uveitis was alsofound. After discharge, she continued with oral and genital ulcers and was treated with infliximab. Despite treatment, headache persists.

Infarto agudo al miocardio en un hombre joven sin ateromatosis coronaria, como forma de presentación de síndrome antifosfolípido primario: Caso clínico / Acute myocardial infarction in a man without coronary atheromatosis and antiphospholipid syndrome: Report of one case

Coronary thrombosis as a manifestation of the antiphospholipid syndrome is very uncommon. We report a 25 year-old male without known cardiovascular risk factors that suffered an acute myocardial infarction as the initial manifestation of the antiphospholipid syndrome. His coronary angiogram demonstrated a single thrombotic lesion in the anterior descending artery without coronary atheromatosis. Anticardiolipin, anti B2 Glycoprotein I antibodies, and lupus anticoagulant were all positive. Besides the usual management of the coronary thrombosis, the patient was treated with permanent oral anticoagulation. Three months later, a CT coronary angiogram showed complete reperfusion of the involved artery.

Doxycycline-induced pseudotumor cerebri.

Tetracyclines are a commonly prescribed medication for the treatment of acne vulgaris that are associated with pseudotumor cerebri (PTC). With doxycycline specifically, however, the incidence of PTC is very rare. A patient was using oral doxycycline and topical retinoids for acne, and within two months she developed PTC. This case illustrates that despite the rarity of doxycycline-induced PTC, patients and physicians should be aware of this possibility. Furthermore, in the setting of new-onset headaches or visual changes, early ophthalmologic examination for papilledema is recommended for early diagnosis.

Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy.

Intracellular pathogens survive by evading the host immune system and accessing host metabolic pathways to obtain nutrients for their growth. Mycobacterium leprae, the causative agent of leprosy, is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Although fatty acids and phospholipids accumulate in the lesions of individuals with the lepromatous (also known as disseminated) form of human leprosy (L-lep), the origin and significance of these lipids remains unclear. Here we show that in human L-lep lesions, there was preferential expression of host lipid metabolism genes, including a group of phospholipases, and that these genes were virtually absent from the mycobacterial genome. Host-derived oxidized phospholipids were detected in macrophages within L-lep lesions, and 1 specific oxidized phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphorylcholine (PEIPC), accumulated in macrophages infected with live mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids both inhibited innate immune responses, and this inhibition was reversed by the addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL from patients with L-lep. The accumulation of host-derived oxidized phospholipids in L-lep lesions is strikingly similar to observations in atherosclerosis, which suggests that the link between host lipid metabolism and innate immunity contributes to the pathogenesis of both microbial infection and metabolic disease.

Effect of combined antisense oligodeoxynucleotides directed against the human papillomavirus type 16 on cervical carcinoma cells.

BACKGROUND: Cervical cancer is highly associated with human papillomavirus (HPV) E6 and E7 gene expression. We have previously reported two antisense oligodeoxynucleotides (AS-ODNs) directed against adjacent targets within the HPV-16 E6/E7 mRNA (419 and 434), each able to downregulate HPV-16 E6/E7 mRNA in vitro and in vivo and to specifically inhibit tumor cell growth in culture and animal models. METHODS: Towards potential clinical application and improved in vivo performance, we analyzed the effect of the combined treatment of 419-434 AS-ODNs on the anchorage independent growth (AIG) of HPV-16-positive cervical carcinoma cell lines. RESULTS: We found similar responses between combined 419-434 and individual AS-ODNs treatments in RNaseH assays, cell uptake, and in vivo degradation of HPV-16 E6/E7 transcripts. Moreover, the combined use of 419-434 AS-ODNs resulted in additive AIG inhibition of CaSki and SiHa cells, similar to that obtained with equivalent doses of the individual AS-ODNs. CONCLUSIONS: By using a combined treatment, it may be possible to overcome the potential mutations frequently reported within HPV-16 genome, thus improving the potential application of 419 and 434 AS-ODNs as a therapeutic alternative for cervical cancer.

MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureus.

MyD88 is an important signaling adaptor for both TLR and IL-1R family members. Here, we evaluated the role of TLR2/MyD88 and IL-1R/MyD88 signaling in host defense against S. aureus by using a cutaneous infection model in conjunction with bioluminescent bacteria. We found that lesions of S. aureus-infected MyD88- and IL-1R-deficient mice were substantially larger with higher bacterial counts compared with wild-type mice. In contrast, TLR2-deficient mice had lesions that were only moderately larger with minimally higher bacterial counts. In addition, MyD88- and IL-1R- but not TLR2-deficient mice had severely decreased recruitment of neutrophils to the site of infection. This neutrophil recruitment was not dependent upon IL-1R/MyD88 signaling by recruited bone marrow-derived cells, suggesting that resident skin cells utilize IL-1R/MyD88 signaling to promote neutrophil recruitment.

Mielolipoma de la glándula suprarrenal sintomático. Presentación de un caso y revisión de la literatura / Suprarenal symptomatic mielolipoma. clinical case and literature review

El mielolipoma de la glándula suprarrenal es un tumor raro, benigno, endocrinológicamente inactivo, cuya estructura histológica consiste de tejido adiposo maduro con focos de células hematopoyéticas. La mayoría de los casos reportados son pequeños y asintomáticos, descubiertos en forma incidental. Presentamos el caso de un paciente del sexo femenino cuyo diagnóstico fue establecido clínicamente al presentar sintomatología dolorosa y corroborado con estudios de imagen. Se presenta el manejo quirúrgico y la evolución postoperatoria. Se efectúa una revisión de las características clínicas de estos tumores, así como su perfil por imagen y opciones de tratamiento.

Hipoplasia dérmica focal en un paciente del sexo masculino: análisis de los mecanismos hereditarios implicados / Focal derman hypoplasia in a male: case report and genetic mechanisms analysis

Introducción. La hipoplasia dérmica focal o síndrome de Goltz es una displasia que afecta tejidos de origen ectodérmico y mesodérmico; muestra herencia dominante ligada al cromosoma X con latelidad in utero para los varones y en las mujeres presenta expresividad variable. Los varones afectados han correspondido a los primeros casos en la familia, por lo que se ha postulado una mutación de media cromátide en estadios tempranos de la embriogénesis con el fin de explicar el mosaico somático y germinal presente en los pacientes. Caso clínico. Se describe el caso de un varón afectado con una genodermatosis caracterizada por hipoplasia de dermis que sigue las líneas de blaschko, talla baja, microcefalia, asimetría facial, microftalmía derecha, persistencia de membrana pupilar, camptodactilia, sindactilia cutánea, hipotricosis, displasia ungueal e hipoplasia de esmalte. Se discuten los mecanismos hereditarios implicados con fines de asesoramiento genético en varones afectados. Conclusión para fines de asesoramiento genético, los riesgos para hipoplasia dérmica focal, sobre todo en casos esporádicos, deben establecerse en base a herencia dominante ligada al cromosoma X, a menos que el árbol genealógico sugiera otro patrón de transmisión hereditaria

Estudio comparativo entre la plastias tubaricas laparoscopicas y las microquirurgicas / Comparative study between the laparoscopic tube plastics and the microsurgical

El objetivo de este trabajo es comparar los resultados obtenidos, en cuanto a permeabilidad tubarica, embarazos y complicaciones se refiere, en un grupo de mujeres con lesiones tubaricas consideradas como la causa de su infertilidad. Para ello se revisan las historias clinicas de 109 pacientes atendidas en la consulta de infertilidad del Hospital Ginecoobtetrico Docente "Ramon Gonzalez Coro" y a quienes se les practico plastia tubarica por laparotomia (45 casos) o por laparoscopia (64 casos). En las laparotomias se utilizaron los mas modernos recursos (laser, microscopio quirurgico, etc). Aunque los grupos no se seleccionaron aleatoriamente, resultaron comparables por sus caracteristicas de edad y tipo de infertilidad y de lesion. Los resultados de ambas tecnicas fueron buenas en cuanto a permeabilidad tubarica y a embarazos normales alcanzados. La cifra de embarazos ectopicos fue de 9,5 vs 5,7

Prolactin, a neuroimmunomodulator implicated in the pathogenesis of rheumatic diseases

A prolactina (PRL) tem importantes propriedades imunorreguladoras e pode desempenhar algum papel na patogenia e expressao de certas doenças auto-imunes. A PRL é capaz de restaurar a imunocompetência em ratos e hipofisectomizados, é co-mitogênica em linfócitos murinos e humanos, induz a formaçao de receptores celulares de superfície para IL-2 e modula a expressao de vários genes relacionados a fatores de crescimento. A PRL também estimula a produçao de anticorpos. Por seu turno, mediadores imunes e inflamatórios estimulam a secreçao de hormônios pituitários. Os linfócitos podem produzir proteínas PRL-símiles biologicamente ativas e têm sido descritos receptores PRL-específicos nos linfócitos T e B. Além disso, hiperprolactinemia tem sido descrita em um subgrupo de pacientes com lúpus eritematoso sistêmico ativo. Na artrite reumatóide, foi demonstrada secreçao excessiva e supra-regulada de PRL. Altos níveis de PRL também foram encontrados em pacientes com síndrome de Sjögren primária e síndrome de Reiter. Esses dados sustentam uma interaçao entre PRL e sistema imune e o papel potencial deste hormônio imunorregulador na patogenia de certas doenças auto-imunes