Different Immunologic Profiles Are Associated With Distinct Clinical Phenotypes in Longitudinally Observed Patients With Systemic Lupus Erythematosus.

OBJECTIVE: The aim of this study was to determine the immunologic profile associated with disease flares in patients with systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following a flare. METHODS: Multiparameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 patients with clinically quiescent SLE, and 46 patients with SLE experiencing a flare at baseline and at 6- and 12-month follow-up visits. Unsupervised clustering was used to identify patients with similar immune profiles and to track changes over time. Parametric or nonparametric statistics were used when appropriate to assess the association of cellular phenotypes with clinical and laboratory parameters. RESULTS: Five clusters of patients were identified that variably contained patients with active and quiescent SLE, and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age-associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow-up. In contrast, patients who had increased T helper (Th ) cells in the absence of B cell changes, or who had increased Th 1 cells and innate immune populations, mostly developed quiescent SLE on follow-up. A significant proportion of patients with SLE had depletion of many immune populations at flare and only showed increases in these populations post-flare. CONCLUSION: Cellular phenotyping of patients with SLE reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment.

Systemic lupus erythematosus and damage: What has changed over the past 20 years?

The young age of onset and chronic/relapsing nature of systemic lupus erythematosus (SLE) make SLE patients prone to develop and accrue organ damage as a result of long-standing disease activity and side effects of treatment. There is a growing interest in objectifying damage and identifying its risk factors. Still, the lack of therapeutic alternatives has led to difficulties in avoiding immunosuppressives particularly corticosteroids, which have been implicated in a large spectrum of organ damage in SLE patients. Moreover, it continues to be very challenging to determine what actually causes damage in different organ-systems. Cardiovascular disease continues to be one of the leading types of damage in patients with SLE, reported as early as 1976. Since then, many researchers have focused on identifying SLE or treatment-related and traditional risk factors. The same considerations are valid for other conditions, such as the occurrence of metabolic syndrome, osteoporosis, avascular necrosis, susceptibility to infections, etc. On the other hand, diverse risk factors contribute to the development of chronic kidney disease (CKD) in SLE. Most evidence suggests that high initial levels of serum creatinine, hypocomplementemia, nephrotic range proteinuria, concomitant uncontrolled hypertension, Black and Hispanic ancestry, non-adherence to treatment, and biopsy findings such as diffuse proliferative lupus nephritis (LN), a high chronicity index, tubular atrophy, and tubulointerstitial inflammation are risk factors for progression to end stage renal disease (ESRD) in LN. While cardiovascular disease, CKD and infections are leading causes of mortality in patients with SLE, hospitalizations are caused mostly by SLE disease flares and infections. Cognitive impairment and mood disorders are common in SLE but continue to impose a challenge on how to measure, manage and decipher the underlying pathogenesis. Nevertheless, they have a great impact on SLE patients' health-related quality of life (HRQoL) and social functioning. Also, skin manifestations, such as alopecia and scaring, cataracts, and sicca symptoms result in a significant decrease in HRQoL. In light of recent developments in SLE treatment, we can expect to enter a period of new-age targeted therapies that will enable us to reduce disease activity and glucocorticoid usage further and positively alter the trajectory of damage development and accrual in SLE.

Interferon and interferon-induced cytokines as markers of impending clinical progression in ANA+ individuals without a systemic autoimmune rheumatic disease diagnosis.

BACKGROUND: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+ individuals and investigated their utility as biomarkers of clinical progression. METHODS: A total of 280 subjects were studied, including 50 ANA- healthy controls, 160 ANA+ individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+ individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. RESULTS: Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+ individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. CONCLUSION: Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+ individuals at high risk of imminent symptomatic progression.

Elevated Levels of Interferon-α Act Directly on B Cells to Breach Multiple Tolerance Mechanisms Promoting Autoantibody Production.

OBJECTIVE: Elevated levels of serum interferon-α (IFNα) and the disruption of B cell tolerance are central to systemic lupus erythematosus (SLE) immunopathogenesis; however, the relationship between these 2 processes remains unclear. The purpose of this study was to investigate the impact of elevated IFNα levels on B cell tolerance mechanisms in vivo and determine whether any changes observed were due to the direct effect of IFNα on B cells. METHODS: Two classical mouse models of B cell tolerance were used in conjunction with an adenoviral vector encoding IFNα to mimic the sustained elevations of IFNα seen in SLE. The role of B cell IFNα signaling, T cells, and Myd88 signaling was determined using B cell-specific IFNα receptor-knockout, CD4+ T cell-depleted, or Myd88-knockout mice, respectively. Flow cytometry, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, and cell cultures were used to study the effects of elevated IFNα on the immunologic phenotype. RESULTS: Elevation of serum IFNα disrupts multiple B cell tolerance mechanisms and leads to autoantibody production. This disruption was dependent upon B cell expression of IFNα receptor. Many of the IFNα-mediated alterations also required the presence of CD4+ T cells as well as Myd88, suggesting that IFNα acts directly on B cells to modify their response to Myd88 signaling and their ability to interact with T cells. CONCLUSION: The results provide evidence that elevated IFNα levels act directly on B cells to facilitate autoantibody production and further highlight the importance of IFN signaling as a potential therapeutic target in SLE.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Altered Balance of Pro-Inflammatory Immune Cells to T Regulatory Cells Differentiates Symptomatic From Asymptomatic Individuals With Anti-Nuclear Antibodies.

Systemic Autoimmune Rheumatic Diseases (SARDs) are characterized by the production of anti-nuclear antibodies (ANAs). ANAs are also seen in healthy individuals and can be detected years before disease onset in SARD. Both the immunological changes that promote development of clinical symptoms in SARD and those that prevent autoimmunity in asymptomatic ANA+ individuals (ANA+ NS) remain largely unexplored. To address this question, we used flow cytometry to examine peripheral blood immune populations in ANA+ individuals, with and without SARD, including 20 individuals who subsequently demonstrated symptom progression. Several immune populations were expanded in ANA+ individuals with and without SARD, as compared with ANA- healthy controls, particularly follicular and peripheral T helper, and antibody-producing B cell subsets. In ANA+ NS individuals, there were significant increases in T regulatory subsets and TGF-ß1 that normalized in SARD patients, whereas in SARD patients there were increases in Th2 and Th17 helper cell levels as compared with ANA+ NS individuals, resulting in a shift in the balance between inflammatory and regulatory T cell subsets. Patients with SARD also had increases in the proportion of pro-inflammatory innate immune cell populations, such as CD14+ myeloid dendritic cells, and intermediate and non-classical monocytes, as compared to ANA+ NS individuals. When comparing ANA+ individuals without SARD who progressed clinically over the subsequent 2 years with those who did not, we found that progressors had significantly increased T and B cell activation, as well as increased levels of LAG3+ T regulatory cells and TGF-ß1. Collectively, our findings suggest that active immunoregulation prevents clinical autoimmunity in ANA+ NS and that this becomes impaired in patients who progress to SARD, resulting in an imbalance favoring inflammation.

Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody-positive individuals.

OBJECTIVE: We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals. METHODS: Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. RESULTS: We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not. CONCLUSION: Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.

Enfermedad de Still del adulto: características clínicas y pronóstico de una cohorte de pacientes colombianos / Adult Still disease: Clinical features and prognosis in a cohort of Colombian patients

Resumen Introducción. La enfermedad de Still del adulto (ESA) es una condición médica poco frecuente que puede presentar complicaciones graves; sin embargo, aún no se conocen con claridad sus factores de riesgo, sus factores pronósticos, ni los aspectos asociados a las recaídas y a la refractariedad a esteroides en individuos con esta condición. Objetivos. Describir el comportamiento clínico de la ESA y determinar los factores asociados a la refractariedad a esteroides, a recaídas y a complicaciones en pacientes con esta enfermedad. Materiales y métodos. Estudio retrospectivo de cohortes que incluyó 45 pacientes diagnosticados con ESA entre enero de 2007 y enero de 2017 en 2 hospitales de referencia. Se presentan medidas de resumen. Se realizaron dos análisis de regresión logística para identificar posibles factores que expliquen la refractariedad a esteroides, las recaídas y el desarrollo de complicaciones en la población de estudio. Resultados. La edad promedio de los participantes fue 42.13±15.8 años. De los 45 pacientes incluidos, 23 (51.1%) eran mujeres, a 42 (93.3%) se le prescribieron esteroides, y, de estos, 13 (32%) se consideraron refractarios a esteroides. Se presentaron complicaciones en 12 (26.7%) individuos y su frecuencia fue mayor en pacientes con temperatura máxima >39°C. Finalmente, 33 (73.3%) pacientes tuvieron un seguimiento mayor a 1 año, de los cuales, 17 (37.8%) presentaron recaídas, las cuales fueron más frecuentes en individuos refractarios a esteroides o con esplenomegalia. Conclusión. Los pacientes que recibieron cualquier tipo de terapia biológica fueron más refractarios a esteroides; por su parte, la refractariedad a esteroides y la esplenomegalia se asociaron a un mayor número de recaídas, y la temperatura >39°C se asoció a al desarrollo de complicaciones.

Abstract Introduction: Adult Still disease (ASD) is a rare disorder that can lead to serious complications; however, risk factors associated with the development of this disease, its prognostic factors, and aspects related to relapse and steroids refractoriness in individuals with this condition are not yet clearly known. Objectives: To describe the clinical behavior of ASD and determine factors associated with steroid refractoriness, relapse, and complications in patients with this condition. Materials and methods: A retrospective cohort study was conducted in 45 patients diagnosed with ASD between January 2007 and January 2017 in 2 reference hospitals. Summary statistics are presented. In addition, two logistic regression analysis were conducted in order to identify possible factors explaining steroid refractoriness, relapses, and the development of complications in the study population. Results: Participants' average age was 42.13 ± 15.8 years. Out of the 45 patients, 23 (51.1%) were women, 42 (93.3%) were prescribed steroids, and of these, 13 (32%) were considered as steroid refractory. Complications were observed in 12 individuals (26.7%), and their frequency was higher in patients whose maximum body temperature was higher than 39°C. Finally, 33 (73.3% patients had a follow-up greater than 1 year, of which 17 (37.8%) suffered relapses; in addition, relapses were more frequent in patients who were steroid refractory or those with splenomegaly. Conclusion: Patients who were prescribed any type of biological therapy were more steroid refractory. On the other hand, steroid refractoriness and splenomegaly were associated with a higher frequency of relapses, while having a body temperature >39°C was associated with developing complications.

Noninfective endocarditis in microscopic polyangiitis: Report of a case with a successful response to immunosuppressive therapy. / Endocarditis no infecciosa en poliangitis microscópica: reporte de un caso con respuesta exitosa a inmunosupresión.

Although antineutrophil cytoplasmic antibody (ANCA) vasculitis has a variety of clinical manifestations, valvular compromise is not common, especially in anti-myeloperoxidase (anti-MPO) antibody (perinuclear [P]-ANCA) vasculitis. We report the case of a 38-year-old woman with ANCA-associated vasculitis who was diagnosed with valve vegetation, that resolved with immunosuppressive therapy.

Microangiopatía trombótica en Lupus Eritematoso Sistémico: a propósito de tres casos / Thrombotic microangiopathy in Systemic Lupus Erythematosus: three cases report

RESUMEN Se describen tres casos de pacientes con lupus y microangiopatía. Los casos descritos representan las principales condiciones asociadas a lupus que pueden generar anemia microangiopática, como son: anemia hemolítica microangiopática, síndrome antifosfolípido con microangiopatía localizada y síndrome antifosfolípido catastrófico. La alta mortalidad que conlleva la anemia microangiopática, sin el tratamiento oportuno, hace necesario motivar a los clínicos a conocer ampliamente la enfermedad para poder reconocerla prontamente.

SUMMARY In this article, we describe three cases of lupic patients that developed microangiopathy. Those cases represent the principal etilogies of microangiopathy in Lupus such as, microangiopathic haemolytic anaemia and antiphospholipid syndrome with and without castastrofic manifestations. The clinicians must know deeply about this condition to recognize it in a timely manner.

Uso de inhibidores directos del factor Xa en síndrome antifosfolípido: una serie de 7 casos / Use of factor Xa inhibitors in antiphospholipid antibodies syndrome: A serie of 7 cases

RESUMEN Introducción: El síndrome antifosfolípido se caracteriza por la presencia de anticuerpos contra fosfolípidos de membrana y manifestaciones clínicas, principalmente trombóticas y obstétricas. Su tratamiento se basa en la anticoagulación indefinida, generalmente con warfarina, la cual, por diversos factores, no siempre es factible por lo que es necesario el uso de terapias alternativas. Objetivo: Describirla experiencia con rivaroxabán en pacientes con síndrome antifosfolípido. Materiales y métodos: Estudio descriptivo en el que se evaluaron pacientes que cumplieron los criterios de Sydney de 2006 para síndrome antifosfolípido y que recibieron anticoagulación con rivaroxabán a dosis de 20 mg día en 2 hospitales de referencia en Medellín (Colombia), entre enero de 2012 y abril de 2015. Resultados: Se incluyeron 7 pacientes con una media de edad de 36,6 ± 10,8 arios (rango: 2355). De estos, 4 individuos tenían trombosis venosa, 5 trombosis arteriales, 5 anticuerpos anticardiolipinas positivos, 3 anticoagulante lúpico positivo, 2 pacientes tenían anti-f32 glicoproteína positivo y un paciente triple positividad de anticuerpos. La mediana de utilización de la warfarina fue de 15 meses (rango: 1-36). Las razones para el inicio de rivaroxabán fueron: sangrado (n = 2), rango subterapéutico de anticoagulación (n = 2), toxicodermia (n = 1), intolerancia gastrointestinal (n = 1) y retrombosis (n = 1). El tiempo de uso fue 17,9 ± 13,4 meses (rango: 3-34) y durante el periodo de seguimiento no se presentaron eventos adversos, pero sí 2 episodios nuevos de trombosis. Conclusión: El uso de inhibidores del factor Xa en una serie de pacientes con síndrome antifosfolípido e imposibilidad para el uso de warfarina mostró un adecuado perfil de seguridad; no obstante, hubo 2 episodios recurrentes de trombosis.

ABSTRACT Background: Antiphospholipid syndrome is an autoimmune disease with antibodies against membrane phospholipids with mainly thrombotic and/or obstetric manifestations. Its treatment is generally based on indefinite anticoagulation, usually with warfarin, and which, for various factors, is not always feasible, making it necessary to use alternative therapies. Objective: To describe the experience with rivaroxaban in patients with antiphospholipid syndrome. Materials and methods: A descriptive study was conducted on subjects that met the 2006 Sydney criteria for antiphospholipid antibodies syndrome and received anticoagulation with rivaroxaban at 20mg daily dose in 2 reference hospitals in Medellin, Colombia, between January 2012 and April 2015. Results: The study included 7 patients, with a mean age of 36±10.8 years (range 23-55). Four patients had venous thrombosis, 5 arterial, 5were positive for anticardiolipin antibodies, 3 reactive to lupus anticoagulant, 2 anti-β2 glycoprotein positive subjects, and one patient had triple antiphospholipid antibody positivity. The median time of warfarin use was 15 months (RIQ 1-36). The reasons for starting rivaroxaban were: bleeding (n = 2), sub-therapeutic coagulation ranges (n = 2), toxicoderma, gastrointestinal intolerance, and re-thrombosis (n = 1, each). The time of use was 17.9±13.4 months (range: 3-34). There were 2 recurrent cases of thrombosis during follow-up, and no adverse events. Conclusion: The use of factor Xa inhibitors in a series of patients with antiphospholipid syndrome and unable to use warfarin showed an adequate safety profile; however, 2 recurrent episodes of venous thrombosis occurred.

Concordance and correlation of activity indices in patients with rheumatoid arthritis in northwestern Colombia: A cross-sectional study.

AIM: To determine the correlation and concordance between different clinimetric scores in patients with rheumatoid arthritis in two high-complexity reference centers in northwestern Colombia. METHOD: A cross-sectional study in adults diagnosed with rheumatoid arthritis was conducted according to the 2010 American College of Rheumatology and European League Against Rheumatism Classification Criteria, between January and June, 2013. The correlation was evaluated using Spearman's correlation coefficient, and concordance with quadratic weighted kappa with the respective confidence intervals, for which patients were classified into different categories of disease activity. RESULTS: One hundred patients were included, of whom 83% were women; 58 and 75% received methotrexate and glucocorticoids, respectively. Most individuals were in remission or low activity. High correlations between Disease Activity Score of 28 joints - erythrocyte sedimentation rate (DAS28-ESR) values with DAS28 C-reactive protein and Simple Disease Activity Index (SDAI) with Clinical Disease Activity Index (P < 0.0001; r = 0.82 and r = 0.86, respectively) were observed; likewise, the scores obtained with different indices correlated well with gold standard values for remission (SDAI), where the correlation with DAS28-ESR was slightly lower. Excellent concordance among all clinimetric scores was observed, although it was lower among DAS28-ESR and SDAI. CONCLUSION: Clinimetric indices had high concordance and correlation, especially for rheumatoid arthritis patients in remission or low disease activity, without being interchangeable among them.

Síndrome de Gardner-Diamond como diagnóstico diferencial de lupus / Gardner-Diamond syndrome as a differential diagnosis of lupus

El síndrome de Gardner-Diamond o púrpura psicógena es una vasculopatía de presunto origen autoinmune que se caracteriza por una reacción cutánea localizada, asociada a situaciones de estrés emocional. Se presenta el caso de una paciente con lesiones equimóticas, dolorosas y de aparición intermitente, relacionadas con diversos eventos estresores, que habían sido manejadas como manifestación de lupus

Gardner-Diamond syndrome or psychogenic purpura is an vasculopathy characterized by a localized cutaneous reaction, associated with episodes of emotional stress or mental illness as trigger factors. A case of a female patient with multiple, intermittent, nodular, ecchymotic and painful lesions related to various stressing events that was treated as lupus is reported below

Coexistencia de neuropatía periférica secundaria a intoxicación crónica por plomo y polimiositis: reporte de caso / Co-existence of peripheral neuropathy secondary to lead poisoning and chronic polymyositis: Case report

Se reporta el caso de un hombre de 47 arios con intoxicación crónica por plomo, secundaria a exposición laboral de 5 años, con sintomatología típica de saturnismo. Consultó por debilidad muscular generalizada, disfagia y parestesias en extremidades. Se documentaron altos niveles de plomo en sangre, asociados a neuropatía periférica, confirmada por electromiografía, y disminución de la fuerza muscular en cintura escapular y pélvica (deltoides y vasto medial), así como atrofia de músculos del cuello (flexores y extensores) manifestada como cefaloparesia. Adicional al cuadro de saturnismo se diagnosticó miopatía inflamatoria con base en la elevación de enzimas musculares, miositis por resonancia magnética nuclear y biopsia muscular compatible, siendo, hasta donde se sabe, el primer reporte conocido de la coexistencia de estas 2 enfermedades

A case is presented on a 47-year-old man with chronic lead poisoning with typical symptoms after 5 years of occupational exposure. He consulted for generalised muscle weakness, early dysphagia, cephaloparesia, and paresthesias in upper and lower limbs. He also had atrophy and decreased proximal muscle strength (deltoid and medial vast) and in both flexor and extensor muscles of the neck. He had a history of high blood lead levels and peripheral neuropathy documented by electromyography. In addition to the diagnosis of lead poisoning, inflammatory myopathy was confirmed based on muscle enzyme elevation, muscular inflammation in magnetic resonance imaging, and typical findings in a muscle biopsy. To our knowledge, this is the first report where both conditions are documented in one patient

Pathophysiological Relationship between Infections and Systemic Vasculitis.

The development of autoimmune disorders requires a combination of genetic, immunological, and environmental factors. Infectious agents, such as viruses and bacteria, can trigger autoimmunity through different mechanisms, and for systemic vasculitis in particular, microbial agents have been suggested to be involved in its pathogenesis. Although the exact mechanisms have not been fully elucidated, different theories have been postulated. This review considers the role of infections in the etiology of primary vasculitis, emphasizing their related immunological events.

Predictive factors for low rate of remission in a population of Colombian patients with severe proliferative lupus nephritis.

The objective of this study is to determine the predictive risk factors of failure to achieve remission within 12 months in a group of patients with proliferative lupus nephritis from Northwestern Colombia. Pragmatic clinical study with retrospective analysis was conducted. We included subjects with systemic lupus erythematosus as defined by the American College of Rheumatology with biopsy-proven nephritis. We assessed 149 patients, with 84 % female. Age at diagnosis of systemic lupus erythematosus is 24.7 years (16-31). The time between diagnosis of lupus erythematosus and proliferative nephritis is 2 months (0-35.5). ISN/RPS 2003 histologic classification types are the following: IV (63.8 %), III (13.4 %), V + III (3.3 %), and V + IV (3.3 %). Activity index is 6.18 ± 4.55 and chronicity index is 1 (0-3). The result of 24-h proteinuria is 2000 mg (667-4770) and baseline creatinine is 0.9 mg/dL (0.7-1.3). Induction therapy includes corticosteroids (100 %), cyclophosphamide (74.1 %), and mycophenolate mofetil (25.9 %). At 12 months, 40.7 % of individuals failed to attain partial or complete remission. Elevated creatinine (p = 0.0001) and 24-h proteinuria greater than 1500 mg (p = 0.0011) were basal predictors of failure to attain partial or complete remission by bivariate analysis. Similar results were obtained in multivariate analysis: Baseline creatinine elevation (OR 3.62, 95 % CI, 1.59-8.23; p = 0.002) and 24-h proteinuria greater than 1500 mg (OR 3.62, 95 % CI, 1.29-10.13; p = 0.014) were independent predictors of failure to achieve partial or complete remission. At 12 months, 40.7 % of patients did not attain partial or complete remission. Baseline elevated creatinine and 24-h proteinuria over 1500 mg were predictors for poor response.

Anemia hemolítica microangiopática en lupus eritematoso sistémico: revisión narrativa de la literatura / Microangiopathic hemolytic anemia in systemic lupus erythematosus: narrative review

El espectro clínico de los trastornos microangiopáticos es muy amplio y se necesitade una gran habilidad clínica para determinar el origen, especialmente en el pacientecon lupus eritematoso sistémico, en quien no solo se debe considerar púrpura trombocitopénicatrombótica asociada, sino también: síndrome antifosfolípido; generalmente del tipocatastrófico; microangiopatía localizada o hipertensión maligna.Objetivo: Describir, de acuerdo con lo reportado en la literatura; la frecuencia, las causas y lascaracterísticas clínicas de la microangiopatía trombótica en lupus eritematoso sistémico.Métodos: Revisión estructurada no sistemática de la literatura.Resultados: Se incluyeron 51 artículos (42 provenientes de la búsqueda en bases de datos y9 referenciados en estos) para la revisión de los aspectos de interés mencionados...

Frecuencia de anticuerpos antipéptido cíclicocitrulinado y factor reumatoide en pacientescon enfermedades reumatológicas de un centrode reumatología, Medellín, Colombia / Frequency of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in patients with rheumatic diseases from a rheumatology outpatient center in Medellin, Colombia

Introducción: El inicio oportuno de la terapia en artritis reumatoide evita el dano˜ articular,y para ello es necesario un diagnóstico precoz. La detección del factor reumatoide y de losanticuerpos antipéptido cíclico citrulinado forma parte del abordaje diagnóstico inicial delpaciente con artritis.Objetivo: Determinar la frecuencia de factor reumatoide y de anticuerpos antipéptido cíclicocitrulinado en pacientes con artritis reumatoide y otras enfermedades reumatológicas, atendidosen un centro ambulatorio de reumatología, en Medellín, Colombia.Métodos: Evaluamos la presencia de factor reumatoide y de anticuerpos antipéptido cíclicocitrulinado en 246 sujetos (64 con artritis reumatoide, 80 con otras enfermedades reumatológicas,61 con osteoartritis y 41 sanos o con fibromialgia).Resultados: En los pacientes con artritis reumatoide la frecuencia de factor reumatoide yde anticuerpos antipéptido cíclico citrulinado y doble positividad fue: 86, 83 y 80%, respectivamente;y en otras enfermedades reumatológicas: 12,5%; 6% y 1%. Ningún sujeto confibromialgia o sano resultó positivo para antipéptido cíclico citrulinado, pero hasta un 5%presentó positividad para factor reumatoide...

IntroductionThe initiation of therapy in rheumatoid arthritis prevents joint damage, but this requires an early diagnosis. The detection of rheumatoid factor and anti-cyclic citrullinated peptide is part of the initial diagnostic approach of patients with arthritis.ObjectiveTo determine the frequency of rheumatoid factor and anti-cyclic citrullinated peptide in patients with rheumatoid arthritis and other rheumatic diseases in patients of a rheumatology outpatient center in Medellin, Colombia.MethodsAn evaluation is made of the presence of rheumatoid factor and anti-cyclic citrullinated peptide in 246 subjects (64 with rheumatoid arthritis, 80 with other rheumatic diseases, 61 with osteoarthritis and 41 healthy or with fibromyalgia).ResultsIn rheumatoid arthritis patients the frequency of rheumatoid factor, anti-cyclic citrullinated peptide, and double positivity (rheumatoid factor and anti-cyclic citrullinated peptide simultaneously) was: 86%, 83% and 80%, respectively, and in other rheumatologic diseases it was: 12.5%, 6%, and 1%, respectively. No subjects with fibromyalgia, or healthy, tested positive for anti-cyclic citrullinated peptide, but up to 5% showed positivity for rheumatoid factor.ConclusionThe possibility of positivity for rheumatoid factor and anti-cyclic citrullinated peptides in diseases other than rheumatoid arthritis and in healthy people should be taken into account, and particularly rheumatoid factor...

Necrosis cutánea extensa secundaria a síndromeantifosfolípido en un paciente con infección por el virusde la inmunodeficiencia humana: reporte de caso / Extensive skin necrosis secondary to antiphospholipid syndrome in an HIV infected patient: A case report

(AU)Aunque un alto porcentaje de pacientes con infección por el virus de la inmunodeficienciahumana tienen anticuerpos antifosfolípidos, la expresión clínica como síndrome antifosfolípidoes poco frecuente. La necrosis cutánea extensa es una de las principalescaracterísticas del síndrome antifosfolípido asociado a esta infección; la piedra angularde su tratamiento consiste en anticoagulación; en casos refractarios, se ha utilizadorituximab y plasmaféresis. Se presenta el caso de un paciente con infección por el virusde la inmunodeficiencia humana quien presentó necrosis cutánea extensa refractaria amúltiples terapias, en el contexto de un síndrome antifosfolípido...

Although a high percentage of patients infected with human immunodeficiency virus have antiphospholipid antibodies, clinical expression as antiphospholipid syndrome is rare. Extensive skin necrosis is one of the main features of antiphospholipid syndrome associated with this infection. The basis of the treatment is anticoagulation, with rituximab and plasmapheresis has being used inrefractory cases. A case is presented on a patient with human immunodeficiency virus infection, who, in the context of antiphospholipid syndrome, presented with extensive skin necrosis refractory to multiple therapies.

Plasmaféresis y recambio terapéutico de plasmaen enfermedades autoinmunes: indicaciones, complicacionesy desenlaces. Descripción de una serie de casos / Plasmapheresis and therapeutic plasma exchange in autoimmune diseases: indications, complications and outcomes. A description of a case series

Introducción: El intercambio terapéutico de plasma y la plasmaféresis son procedimientosque permiten la eliminación de macromoléculas nocivas y que están indicados en algunostrastornos autoinmunes cuando está en peligro la vida o un órgano vital.Objetivos y métodos: Describir la experiencia con el uso de la plasmaféresis y el intercambioterapéutico de plasma en patologías autoinmunes en un hospital universitario de cuartonivel de complejidad, centro de referencia. Estudio descriptivo, retrospectivo, de una seriede casos.Resultados: Se incluyeron 93 pacientes; 67 tenían enfermedades autoinmunes: neurológicas(66%), hematológicas (18%) y reumatológicas (12%). El 82% del grupo tuvo una respuestafavorable (61% completa y 21% parcial). La mortalidad global fue del 6%. En el subgrupo deenfermedades reumatológicas, las indicaciones más frecuentes fueron: lupus eritematososistémico y vasculitis asociadas a anticuerpos contra el citoplasma de neutrófilo (37,5%cada una) por compromisos: respiratorio o neurológico. Las secuelas más importantesfueron neurológicas y renales. El 63% de los sujetos no presentó ningún evento adverso.Conclusiones: Los pacientes que recibieron plasmaféresis o intercambio terapéutico deplasma por enfermedades autoinmunes con una condición crítica que amenaza la vida o unórgano vital presentaron una respuesta favorable que redundó en una mejor supervivenciaa corto plazo; estas terapias son, generalmente, bien toleradas. Se requieren estudios conmayor solidez metodológica, especialmente en las enfermedades reumatológicas...

Background: Therapeutic plasma exchange and plasmapheresis are procedures that allow the removal of harmful macromolecules, and are indicated in some autoimmune disorders, when life or vital organs are in danger.Objectives and Methods: To describe the experience with the use of therapeutic plasmapheresis and plasma exchange in autoimmune diseases in a tertiary reference university hospital. A retrospective descriptive study was conducted on a series of cases.Results: Of the 93 patients included, 67 had autoimmune diseases: neurological (66%), hematological (18%), and rheumatic (12%). A favorable response was observed in 82% of the group (61% complete and 21% partial). Overall mortality was 6%. In the subgroup of rheumatology diseases, the most frequent indications were: systemic lupus erythematosus and vasculitis associated with antibodies against neutrophil cytoplasm (37.5 % each) for respiratory or neurological involvement. The most important sequelae were neurological and renal. No adverse events were reported in 63% of the subjects.Conclusions: Patients receiving therapeutic plasmapheresis or plasma exchange in autoimmune diseases with a critical life-threatening condition or a vital organ involvement had a favorable response that resulted in better short-term survival. These therapies are, generally, well tolerated. Studies with greater methodological soundness, especially in rheumatic diseases, are required...