HLA-DRB1*07:01 and *08:02 Alleles Confer a Protective Effect Against ACPA-Positive Rheumatoid Arthritis in a Latin American Admixed Population.

HLA-DRB1 shared epitope (SE) alleles are important genetic contributors for the risk of developing anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis (RA), particularly in Caucasians. We aimed to analyze the contribution of HLA-DRB1 alleles and single nucleotide polymorphisms (SNPs) within the major histocompatibility complex (MHC) region to the susceptibility to develop ACPA-positive RA in a Latin American (LA) population with admixed ancestry. A total of 289 ACPA-positive RA patients and 510 controls were enrolled in this study. The presence of HLA-DRB1*04:01, *09:01 and *10:01 was increased in ACPA-positive RA patients compared with healthy controls (p < 0.0001, p < 0.001 and p < 0.01, respectively), whereas DRB1*07:01 and *08:02 was associated with a decreased risk of ACPA-positive RA (p < 0.001 and p < 0.01, respectively). These results showed a strong correlation with estimates from studies in Asians but not in Caucasian populations. The present study describes the protective effects of the HLA-DRB1*07:01 and *08:02 alleles in ACPA-positive RA patients in a LA population for the first time. Identifying relationships between HLA-DRB1 alleles and RA is important for identifying disease associations in different ethnic groups in order to reach a better understanding of RA worldwide.

Ignavigranum ruoffiae, a rare pathogen that caused a skin abscess.

INTRODUCTION: Ignavigranum ruoffiae is an extremely rare cause of human infections. CASE PRESENTATION: An 83-year-old male with a painless, ten-day-old, erythematous skin abscess on his left flank, which had showed a purulent discharge for 48 h, was admitted to the Emergency service. He was treated with cephalexin, disinfection with Codex water and spray of rifampicin. Five days later, surgical drainage of the abscess was proposed due to the torpid evolution of the patient. Samples were taken for culture, and antibiotic treatment with trimethoprim-sulfamethoxazole was established. The patient returned after 10 days showing healing of the abscess. Microbiological studies showed a few Gram-positive cocci present as single cells and short chains that grew after 72 h of incubation at 35 °C with CO2 on 5 % sheep blood agar. Colonies presented a strong sauerkraut odour. Initial biochemical test results were negative for catalase, aesculin and bile-aesculin, and positive for pyrrolidonyl arylamidase, leucine aminopeptidase and growth in 6.5 % NaCl broth, which prompted the preliminary identification of Facklamia species or I. ruoffiae. The positive result for arginine deamination and negative result for hippurate hydrolysis, failure to produce acid from mannitol, sucrose, sorbitol or trehalose, plus the distinctive sauerkraut odour identified the organism as I. ruoffiae. The phenotypic identification was confirmed by 16S rRNA gene sequence analysis. The strain seemed to be susceptible to the antimicrobials tested but had decreased susceptibility to carbapenems. CONCLUSION: This case provides more insights into the phenotypic characteristics and antimicrobial resistance profile of I. ruoffiae.

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.

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

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.

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.

An analysis of 372 patients with anterior uveitis in a large Ibero-American cohort of spondyloarthritis: the RESPONDIA Group.

OBJECTIVES: This study analysed the frequency of anterior uveitis (AU) and its correlations in a large cohort of patients with spondyloarthritis (SpA). METHODS: A common protocol of investigation was prospectively applied to 2012 SpA patients in 85 centres from 10 Ibero-American countries. Clinical and demographic variables and disease indexes were investigated. Categorical variables were compared by χ2 and Fisher's exact test, and continuous variables were compared by ANOVA or Kruskal-Wallis test. A value of p<0.05 was considered significant. RESULTS: AU was referred by 372 SpA patients (18.5%). AU was statistically associated with inflammatory low back pain (p<0.001), radiographic sacroiliitis (p<0.001), enthesopathies (p=0.004), urethritis/acute diarrhoea (p<0.001), balanitis (p=0.002), hip involvement (p=0.002), HLA-B27 (p=0.003), and higher C-reactive protein (p=0.001), whilst it was negatively associated with the number of painful (p=0.03) and swollen (p=0.005) peripheral joints, psoriatic arthritis (p<0.001), psoriasis (p<0.001), nail involvement (p<0.001), and dactilitis (p=0.062; trend). No association with gender, race, and indices (disease activity, functionality and quality of life) was observed. Logistic regression showed that ankylosing spondylitis (p=0.001) and HLA-B27 (p=0.083; trend) was significantly associated with AU, while extra-articular manifestations (predominantly psoriasis) were negatively associated (p=0.016). CONCLUSIONS: Anterior uveitis is a frequent extra-articular manifestation in SpA patients, positively associated with axial involvement and HLA-B27 and negatively associated with peripheral involvement and psoriatic arthritis.

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.

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

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.

Haem oxygenase 1 expression is altered in monocytes from patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple functional alterations affecting immune cells, such as B cells, T cells, dendritic cells (DCs) and monocytes. During SLE, the immunogenicity of monocytes and DCs is significantly up-regulated, promoting the activation of self-reactive T cells. Accordingly, it is important to understand the contribution of these cells to the pathogenesis of SLE and the mechanisms responsible for their altered functionality during disease. One of the key enzymes that control monocyte and DC function is haem oxygenase-1 (HO-1), which catalyses the degradation of the haem group into biliverdin, carbon monoxide and free iron. These products possess immunosuppressive and anti-inflammatory capacities. The main goal of this work was to determine HO-1 expression in monocytes and DCs from patients with SLE and healthy controls. Hence, peripheral blood mononuclear cells were obtained from 43 patients with SLE and 30 healthy controls. CD14(+) monocytes and CD4(+) T cells were sorted by FACS and HO-1 expression was measured by RT-PCR. In addition, HO-1 protein expression was determined by FACS. HO-1 levels in monocytes were significantly reduced in patients with SLE compared with healthy controls. These results were confirmed by flow cytometry. No differences were observed in other cell types, such as DCs or CD4(+) T cells, although decreased MHC-II levels were observed in DCs from patients with SLE. In conclusion, we found a significant decrease in HO-1 expression, specifically in monocytes from patients with SLE, suggesting that an imbalance of monocyte function could be partly the result of a decrease in HO-1 expression.

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.

Genetic and pharmacological modulation of dendritic cell-T cell interactions as a therapeutic strategy for systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by an excessive production of auto-antibodies against double-stranded DNA, nucleosomes, ribonucleoproteins and other nuclear components. Accumulation of self-reactive antibodies leads to immune complex deposition in blood vessels, activation of macrophages and complement, inflammation and subsequent tissue damage in several organs, such as the heart, kidneys, lungs and central nervous system. Although significant progress has been made in the past 30 years of research, no effective specific treatments are currently available. The course of this disease remains unpredictable and patients diagnosed with SLE face long-term treatments with the subsequent economic, social and health burden. From the immunological perspective, SLE is a genetic- and environment-controlled disease that involves almost every constituent of the immune system, including both innate and adaptive immunity. Therefore, several immune cell types and molecules could be susceptible for intervention and modulation to develop more effective and specific treatments. More importantly, such therapies are likely not to induce complete immunosuppression and show reduced side effects on patients. In this article we discuss recent work in the field of SLE pathogenesis with a focus on data that provide clues for therapy design and new treatments.

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.

New World cutaneous leishmaniasis: current challenges in diagnosis and parenteral treatment.

Many physicians in the United States and other nonendemic countries lack familiarity with New World cutaneous leishmaniasis (CL) and fail to include it in their differential diagnosis when seeing patients with suggestive lesions and recent high-risk travel. Moreover, even when the diagnosis of New World CL is considered and confirmed, physicians in the United States still face obstacles in obtaining appropriate treatment. In this report, we present 3 cases of New World CL that were either initially misdiagnosed or faced significant delays in therapy. We also discuss the optimal approach by which to confirm New World CL and to collaborate with professional colleagues at the Centers for Disease Control and Prevention in treating individual patients. In particular, when pentavalent antimonial treatment is needed for treatment, physicians must obtain appropriate diagnostic studies, communicate with experts at the Centers for Disease Control and Prevention, complete necessary paperwork, and obtain approval from their local institutional review board to administer it.

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.(AU)

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.