Caracterización epidemiológica de pacientes con miopatía inflamatoria en un hospital de cuarto nivel en Cali, Colombia / Epidemiological characterization of patients with inflammatory myopathy in a fourth level hospital in Cali, Colombia

Introducción: Las miopatías inflamatorias idiopáticas (MII) constituyen un grupo heterogéneo de enfermedades que comprometen la musculatura esquelética y se manifiestan por debilidad y signos inflamatorios en la biopsia muscular. El objetivo de este estudio es hacer una caracterización epidemiológica de una cohorte de pacientes con MII en una población del suroccidente colombiano. Metodología: De forma retrospectiva, se revisaron las historias clínicas de pacientes con diagnóstico de MII que fueron tratados en un hospital de cuarto nivel de complejidad en Cali, Colombia, entre el 2011 y el 2017. Se recolectaron variables demográficas, clínicas, serológicas y de tratamiento. Resultados: Se identificaron 72 pacientes con MII, mayoritariamente mujeres (n = 54, 75%). La media de edad al inicio de los síntomas fue de 37,11 ± 19,18 años. Las principales MII fueron dermatomiositis (DM) y polimiositis, las cuales se presentaron en 35 (48,6%) y 25 pacientes (34,7%), respectivamente. Veintiocho pacientes (38,8%) presentaban enfermedad autoinmune asociada, siendo el lupus eritematoso sistémico la más frecuente, al presentarse en7 (9,72%) pacientes. La biopsia de músculo se realizó en 25 pacientes (34,7%), mientras que28 (38,8%) tenían anticuerpos antinucleares positivos. La mediana de la creatinfosfoquinasa fue de 877,5 mg/dL (163,5-4.358,3). Sesenta y siete pacientes (93,1%) fueron tratados con glucocorticoides y 18 (25%) con rituximab (RTX) como monoterapia o combinado con otro fármaco inmunosupresor. Conclusiones: La DM es la condición clínica más frecuente, es común en mujeres y se presenta en la cuarta década de vida. Los tratamientos con los que más se obtuvo mejoría clínica fueron los glucocorticoides, seguidos del RTX en monoterapia o combinado con otros inmunosupresores.

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterised by skeletal muscle involvement, manifested by weakness and inflammatory signs in the muscle biopsy. The objective of this article is to describe the clinical, laboratory, and treatment features of a cohort of patients with IIM in southwest Colombia. Methods: A retrospective review was conducted on the medical records of patients diagnosed with IIM treated at a fourth-level complexity hospital in Cali, Colombia, from 2011 to 2017. Demographic, clinical, serological, and treatment data were collected. Results: A total of 72 patients with IIM were identified, mostly women (n = 54,75%). The mean age at onset of symptoms was 37.11 ± 19.18 years. The main subtypes of IIM were dermatomyositis (DM) and polymyositis, occurring in 35 patients (48.6%) and 25 patients (34.7%), respectively. Twenty-eight patients (38.8%) had associated autoimmune disease, with syste mic lupus erythematosus being the most frequent in 7 (9.72%) patients. Muscle biopsy was performed in 25 patients (34.7%), while 28 (38.8%) had positive antinuclear antibodies. The median creatine phosphokinase was 877.5 mg/dL (163.5-4358.3). Sixty-seven patients (93.1%) were treated with glucocorticoids, and 18 (25%) patients were treated with rituximab (RTX) as monotherapy or combined with another immunosuppressant drug. Conclusions: DM is the most frequent subtype of IIM, being common in women and occurring in the fourth decade of life. The most used treatments were glucocorticoids, followed by RTX monotherapy, or combined with other immunosuppressants.

Utility of anti-C1q and anti-nucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia / Utilidad de los anticuerpos anti-C1q y anti-nucleosomas en el lupus eritematoso sistémico y la nefritis lúpica en el suroccidente colombiano

ABSTRACT Introduction: Lupus nephritis (LN) is one of the most prevalent and severe complications of systemic lupus erythematosus (SLE), requiring reliable urine and serum biomarkers to evaluate it. Anti-nucleosome and anti-C1q antibodies are associated with LN in several geographic regions. Also, southwest Colombia has a heterogeneous ethnicity, which motivated the evaluation of the frequency and relationship of such markers with LN in this region. Methods: A cross-sectional study was conducted in a health centre in south-west Colombia in 84 patients diagnosed with SLE (57 without LN; 27 with LN) between 2016 and 2018. Demographic and clinical and laboratory features, including anti-dsDNA, complement, and anti-C1q and anti-nucleosome antibodies were compared in these patients. ELISA immunoassays were performed to measure the antibodies of interest in blood samples. Statistical analysis was carried out using STATA14 software (StataCorp, College Station, Texas, USA). Quantitative variables were summarised as means or medians and compared with Mann-Whitney or Two-sample t test. Categorical variables were shown as proportions, and compared with Chi-squared or Fisher's exact test. Correlation analysis between quantitative variables was calculated using Spearman's correlation. Results: Of all 84 patients, 27 patients had LN, of which 16 (59.2%) had a positive test for anti-nucleosome antibodies and 10 (37%) for anti-C1q antibodies. An association was found between anti-C1q and proliferative forms of LN and newly diagnosed LN. A correlation was found between anti-nucleosome and anti-C1q antibodies, and anti-dsDNA and low serum complement concentrations. Conclusion: Although both markers were found in variable percentages in SLE patients and seem not to be specific markers of LN in our population, anti-C1q was associated with proliferative forms of LN and de novo LN.

RESUMEN Introducción: La nefritis lúpica (NL), una de las complicaciones más frecuentes y graves del lupus eritematoso sistémico (LES), requiere biomarcadores confiables de orina y suero para su evaluación. Los anticuerpos anti-nucleosoma y anti-C1q se asocian con la NL en varias regiones geográficas. En el suroccidente colombiano se asienta una etnia heterogénea, lo que motivó la evaluación de la frecuencia y la relación de dichos marcadores con NL en dicha región. Métodos: Realizamos un estudio transversal en un centro de salud en el suroccidente de Colombia, con 84 pacientes diagnosticados con LES (57 sin NL; 27 con NL) entre los anos 2016 y 2018. Se compararon las características demográficas, clínicas y de laboratorio, incluidos los anticuerpos anti-dsDNA, complemento, anti-C1q y anti-nucleosomas entre estos pacientes. Se realizaron inmunoensayos ELISA para medir los anticuerpos de interés en muestras de sangre. El análisis estadístico se llevó a cabo con el software Stata v.14 (Stata-Corp, College Station, Texas, EE. UU.). Las variables cuantitativas se resumieron como medias o medianas y se compararon con la prueba t de Mann-Whitney o Two-sample t test; las variables categóricas se mostraron como proporciones y se compararon con Chi-cuadrado o con la prueba exacta de Fisher. Para el análisis de correlaciones entre variables cuantitativas se calculó el coeficiente de correlación de Spearman. Resultados: Entre los 84 pacientes, 27 presentaban LN, de los cuales 16 (59,2%) tuvieron una prueba positiva para anticuerpos anti-nucleosoma y 10 (37%) para anticuerpos anti-C1q. Se encontró una asociación entre anti-C1q y formas proliferativas de NL, así como formas recientemente diagnosticadas de NL. Hubo una correlación entre los anticuerpos anti-nucleosoma y anti-C1q y el anti-dsDNA y las bajas concentraciones de complemento sérico. Conclusión: Aunque los 2 marcadores se encontraron en porcentajes variables de pacientes con LES y no parecen ser marcadores específicos de NL en nuestra población, la presencia de anti-C1q se asoció con formas proliferativas de NL y NL de novo.

Rituximab for Inflammatory Myopathies in a Colombian Cohort.

INTRODUCTION/OBJECTIVES: Rituximab (RTX) is a treatment for refractory inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). This study describes the characteristics of patients receiving RTX for myositis in our institution to evaluate its efficacy. METHOD: We collected demographic data from all patients diagnosed with DM or PM who received RTX between 2011 and 2018. Clinical and serological variables (including creatine phosphokinase [CPK] levels) were analyzed. Remission of disease was defined as no evidence of disease activity (active myositis) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. RESULTS: Eighteen patients who had received first-line immunosuppressants were included. Fifteen (83%) had DM, 2 (11%) had PM, 1 had juvenile dermatomyositis, and 14 (77%) were women. All patients received glucocorticoids. Three patients (16.6%) were treated with RTX as monotherapy, and 15 (83.3%) were treated with RTX combined with other immunosuppressants. On average, there were 2 RTX treatment cycles. Improved muscular weakness was found in 13 cases (72%), and improved serum CPK levels were found in 15 cases (83%). Twelve patients (66%) achieved remission. CONCLUSIONS: Most patients experienced an objective improvement, as reflected in their serum CPK values and degree of muscular weakness. This suggests that RTX could be helpful in treating refractory myositis.

Expression of BAFF, APRIL, and cognate receptor genes in lupus nephritis and potential use as urinary biomarkers.

BACKGROUND: B-cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and their receptors BAFF-R, BCMA, and TACI are crucial factors for the survival of B lymphocytes. Recent evidence has also demonstrated the importance of BAFF/APRIL signaling in lupus nephritis (LN). This study evaluated the relationships between LN clinical characteristics and the urinary expression levels of BAFF, APRIL, and cognate receptors to assess their potential value as disease biomarkers. METHODS: Expression levels of these genes were assessed in urine samples collected from systemic lupus erythematosus (SLE) patients before renal biopsy using reverse transcription real-time PCR. RESULTS: Thirty-five patients with LN were included. Most of the patients were female (82.86%) with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 15. BAFF mRNA was detectable in 28.57%, APRIL mRNA in 42.85%, BR3 mRNA in 48.57%, and TACI mRNA in 42.85% of urine samples. On the other hand, urinary (u)BCMA mRNA was not found in any sample. Urinary expression of most biomarkers was detected with greater frequency in class III and IV LN compared to class V LN. The expression level of uBR3 mRNA was correlated with SLEDAI-2K and histological activity index. CONCLUSION: Urinary expression of BAFF/APRIL signaling factors, especially TACI, APRIL, and BR3 mRNAs, may be useful biomarkers for LN.

Correction to: Mortality in patients with systemic lupus erythematosus in Colombia: a case series.

The presentation of data on the Table 3 of the published version of the above mentioned article was incorrect. The heading "Bacterial infections" should be presented under the heading "Infections". The original article has been corrected.

Mortality in patients with systemic lupus erythematosus in Colombia: a case series.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with high mortality rates. This study aimed to describe the main causes of death in a case series of SLE patients attended in a single center in Colombia. METHODS: We conducted a retrospective review and analysis of records of SLE patients who died between January 2011 and June 2017. We extracted the main causes of death and described variables associated with this outcome as well as variables associated with the disease and its treatment. RESULTS: From a total of 1776 patients with SLE, we identified 49 fatal cases (89.8% women, n = 44). The average age at death was 40.6 years (SD 17.4), and patients had a median of 4.5 years (IQR 2-8) of disease duration. The main findings included lymphopenia in 44 patients (89.9%), biopsy-confirmed lupus nephritis (LN)-types IV and VI-in 38 (77.6%), catastrophic antiphospholipid syndrome (CAPS) in 8 (16.3%), and persistent hypocomplementemia (C3 and C4) in 8 (16.3%). The median SLE disease activity index (SLEDAI-2K) score at the time of death was 19 (IQR 11-39). The main cause of death was SLE activity and lupus-induced damage in 22 (44.9%) patients. CONCLUSION: The main causes of death included SLE activity refractory to immunosuppressive treatment, and nosocomial bacterial infections. The patients who died had persistently high SLEDAI scores, types IV and VI LN, associated antiphospholipid syndrome, and persistent hypocomplementemia, requiring severe immunosuppression and prolonged hospitalization.

Therapeutic Plasma Exchange as Management of Complicated Systemic Lupus Erythematosus and Other Autoimmune Diseases.

INTRODUCTION: Autoimmune diseases include a diverse and complex group of pathologies with a broad clinical spectrum due to the production of autoantibodies, which generates multisystemic compromise. Therapeutic plasma exchange (TPE) is a good additive treatment for immunosuppression due to its action over the autoantibodies. OBJECTIVES: To describe the main clinical characteristics and outcomes of patients with systemic lupus erythematosus and other systemic autoimmune diseases managed with TPE. METHODOLOGY: This descriptive retrospective study enrolled patients with systemic autoimmune diseases who received TPE. RESULTS: In total, 66 patients with a median age of 33.5 years (24-53 years) were included; the majority were females [n=51 (77.27%)]. Forty (60.61%) patients were diagnosed with systemic lupus erythematosus. In these cases, the main indication for TPE was diffuse alveolar hemorrhage (DAH; n=20, 30.3%) and neurolupus (n=9, 13.6%). No TPE-related deaths occurred, and the main complication was hemorrhage, without significant differences among the four types of TPE solutions used. The overall outcome was improvement in 41 (62.12%) patients. CONCLUSION: TPE is safe and effective in patients with severe manifestations of autoimmune diseases.

Neurological Involvement as the Initial Manifestation in Primary Sjögren's Syndrome - A Case Report.

BACKGROUND: Sjögren's syndrome is an autoimmune disease characterised by exocrinopathy mainly involving the salivary and lacrimal glands. In addition, it is a multisystemic condition (i.e., affecting multiple organs and systems). Neurological involvement has been reported in ~20% of cases, with peripheral manifestations being the most frequent. METHODS: We analysed four cases in which neurological manifestations were the first symptoms of Sjögren's syndrome. RESULTS: In all four cases, neurological symptoms preceded sicca symptoms. In addition, immunosuppressive treatment with steroids and, in some cases, cyclophosphamide showed improvement. CONCLUSION: Neurological involvement in Sjögren's syndrome is common and often occurs as the first clinical manifestation. Since evidence is limited, more studies are required in order to determine appropriate diagnostic methods and treatments for each manifestation of Sjögren's syndrome.

Systemic Sclerosis at an Intensive Care Unit: A Case Series and Literature Review.

INTRODUCTION: Systemic sclerosis (SSc) is a multisystemic autoimmune disease. Few studies have focused on the outcomes of SSC patients who require intensive care unit (ICU) admission, largely due to the absence of protocols for the optimal management of this disease during an ICU stay. OBJECTIVES: This study aimed to describe the outcomes of a series of SSc patients admitted to the ICU at a single center in Cali, Colombia. METHODS: Case series of SSc patients admitted to the ICU were reviewed. The main outcome was ICU mortality. Statistical analysis was performed with measures of central tendency and proportions. RESULTS: All the patients (n = 14) were female and either middle-aged or elderly; 9 (64%) were diagnosed with diffuse cutaneous sclerosis, and the remaining 5 patients with limited cutaneous sclerosis. Some were readmitted; therefore, the total number of ICU admissions was 21. The principal causes of ICU admissions were non-SSc-related causes (n = 15 [71.4%]). The respiratory system was the most involved on ICU admissions. The ICU mortality rate was 43% (n = 6). CONCLUSIONS: The severity of the disease at ICU admission and comorbidity are independently associated with ICU-related mortality. Furthermore, the optimal management of SSc patients includes accurate detection of SSc-associated organ involvement. More studies involving this category of patients are needed to establish the best effective protocols.

Interpretación de los autoanticuerpos en enfermedades reumatológicas / Interpretation of autoantibodies in rheumatological diseases

RESUMEN Las enfermedades autoinmunes son un grupo de patologías crónicas en las que factores genéticos, ambientales y hormonales contribuyen a su aparición. Además de tener un amplio espectro clínico, la interpretación de los diversos autoanticuerpos y técnicas utilizadas en el laboratorio también son un reto clínico. Dada la complejidad de estas enfermedades, es muy importante apoyarse en las pruebas de laboratorio para establecer un correcto diagnóstico, seguimiento y, en algunos casos inclusive, establecer pronósticos o predicción de la posible aparición de autoinmunidad. Con todo esto se pretende mejorar la calidad de vida de los pacientes disminuyendo la gran morbimortalidad de este grupo de enfermedades, especialmente al diagnosticarlas en etapas tempranas. La mayoría de las enfermedades reumatológicas se caracterizan por la alta producción de autoanticuerpos y reactantes de fase aguda, los cuales están implicados en su fisiopatología produciendo daño directo a nivel sistémico. Entre estas, el lupus eritematoso sistémico, la artritis reumatoide y el síndrome de Sjögren son las más reconocidas. Portales motivos, el objetivo de este trabajo es hacer una revisión que permita guiar tanto a médicos como a personal de laboratorio en la interpretación de los diferentes autoanticuerpos en enfermedades autoinmunes.

ABSTRACT Autoimmune diseases are a group of chronic diseases in which genetic, environmental, and hormonal factors contribute to their appearance. In addition to having a broad clinical spectrum, the interpretation of the various autoantibodies and techniques used in the laboratory is also a clinical challenge. Given the complexity of these diseases, it is very important to rely on the results of laboratory tests to establish a correct diagnosis and follow-up and, in some cases even to establish a prognosis or prediction of autoimmunity. Taking all this into account, it is intended to improve the quality of life of patients by decreasing the increased morbidity and mortality in this group of diseases, especially by early diagnosis. Most rheumatological diseases are characterised by the high production of auto-antibodies and acute phase reactants, which are involved in their pathophysiology, leading to systemic involvement. Among these, the most recognised are, systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. For these reasons, the objective of this project is to present a review that will help both physicians and laboratory personnel in the interpretation of the different autoantibodies in autoimmune diseases.

Anticuerpos anti-DFS70: un nuevo autoanticuerpo útil en la exclusión de patologías autoinmunes / Anti-DFS70 antibodies: A new useful antibody in the exclusion of auto-immune diseases

RESUMEN Los anticuerpos anti-DFS70 (Dense Fine Speckle, peso molecular de 70 kd) son un subgrupo de anticuerpos antinucleares (ANA) de tipo natural, los cuales se manifiestan por un patrón moteado denso fino (DFS) por inmunofluorescencia indirecta. Este se caracteriza por la fluorescencia granular distribuida irregularmente en la interface de los núcleos y de la cromatina. Inicialmente, este anticuerpo fue descrito en pacientes con cistitis intersticial, dermatitis atópica y algunas neoplasias como el cáncer de próstata. Se ha encontrado que sus antígenos actúan directamente contra co-activadores de la transcripción nuclear (LEDGF/p75), codificada por el gen PSP1 y localizado en la región C terminal entre los a.a. 349 y 435. Adicionalmente, se documenta asociación con algunas funciones fisiológicas como la protección contra la apoptosis inducida por estrés, promover la supervivencia de las células epiteliales del cristalino y actuar como cofactor de replicación del virus VIH a través de su interacción con la integrasa viral. En el campo de la autoinmunidad se ha evidenciado recientemente la importancia de este anticuerpo como marcador biológico útil en la discriminación de personas con ANA positivos que no evolucionan a enfermedad autoinmune sistémica (EAI). Lo anterior se ha basado en la observación de que estos anticuerpos son más frecuentes en individuos sanos que en los pacientes con EAI y que los individuos sanos con anti-DFS70 positivo no desarrollaron EAI después de un seguimiento clínico por 4 arios o más. Este artículo revisa la descripción de los anti-DFS70 y su utilidad en la práctica clínica.

ABSTRACT Anti-DFS70 antibodies (Dense Fine Speckled, 70 kd molecular weight) are a sub-group of anti-nuclear antibodies (ANA) that show a fine dense speckled pattern (DFS) by indirect immunofluorescence. This pattern is also recognized by irregularly distributed granular fluorescence at the interface of nuclei and chromatin. This antibody was initially described in patients with interstitial cystitis, atopic dermatitis, and malignancy, such as prostate cancer. These antigens have been found to act directly against co-activators of nuclear transcription (LEDGF/p75) encoded by the PSP1 gene and located in the C-terminal region between the a.a. 349 and 435. Additionally, associations with some physiological functions have been described, such as protection against stress-induced apoptosis, the survival of lens epithelial cells, and acting as a cofactor of HIV replication through its interaction with viral integrase. As regards autoimmunity, recent evidence has also shown the importance of this antibody as a useful biological marker in the discrimination of individuals with positive ANA that do not progress to systemic autoimmune disease (SID). This is based on the observation that these antibodies are more common in healthy individuals than in patients with SID, and that healthy individuals with positive anti-DFS70 did not develop SIDs after a clinical follow-up of four years or more. This article reviews the description of anti-DFS70 and its usefulness in clinical practice.

La expresión de CD64 en neutrófilos, procalcitonina y presepsina sérica son útiles para diferenciar infección de actividad en pacientes con lupus eritematoso sistémico y respuesta inflamatoria patients with systemic lupus erythematosus and inflammatory response / CD64 expression in neutrophils, Procalcitonin and serum presepsina are useful for differentiating infection activity in patients with systemic lupus erythematosus and inflammatory response

Introducción: La diferenciación entre actividad lúpica de infecciones en pacientes con lupus eritematoso sistémico (LES) es difícil debido a una presentación clínica similar. El objetivo es evaluar la utilidad de una serie de biomarcadores para diferenciar infecciones de actividad en pacientes con LES admitidos con respuesta inflamatoria sistémica (SIRS). Métodos: Pacientes con LES y SIRS que consultaron al servicio de urgencias fueron seleccionados. Se realizaron mediciones de diferentes marcadores como procalcitonina, expresión de CD64 de neutrófilos y presepsina al ingreso y fueron comparados con la presencia o no de infección, la cual se consideró presente con cultivos positivos y/o evidencia microbiológica por PCR. Se calculó la sensibilidad y especificidad de cada biomarcador y puntos de corte usando curvas ROC.

Utilidad de la plasmaféresis en pacientes con lupus eritematoso sistémico en un centro de alta complejidad del suroccidente colombiano / Utility of plasma exchange in patients with systemic lupus erythematosus in a centre of high complexity of the Colombian Southwest

Introducción y Objetivo: El lupus eritematoso sistémico (LES) es una enfermedad multiorgánica mediada principalmente por el depósito de complejos inmunes en órganos blanco, los cuales pueden ser removidos rápidamente mediante plasmaféresis, considerándose esta modalidad terapéutica clave para el manejo de pacientes críticos, sumado al tratamiento inmunosupresor. Nuestro objetivo es describir las principales características clínicas y desenlaces de pacientes con LES quienes recibieron manejo con recambio plasmático terapéutico (PEX) en un hospital de alta complejidad del suroccidente colombiano. Métodos: Se realizó un estudio descriptivo, donde se incluyeron pacientes con diagnóstico de LES quienes hayan recibido PEX. Resultados: Un total de 40 pacientes fueron incluidos.

Autoimmune diseases and their relation with immunological, neurological and endocrinological axes.

The immune response is complex, multifactorial, individualized and often unpredictable. There are multiple interconnected systems that allow a balance between physiological autoreactive processes and pathological autoimmunity with consequent organ-specific or systemic autoimmune disease. Based on the concept of the autoimmunity mosaic, up to 50% of autoimmune disorders do not have a clear etiological factor. In order to achieve a clear understanding of the different systems that influence the development of autoimmune diseases, the clinical auto-immunologist needs a dynamic and comprehensive vision of all interconnected pathways that maintain a precise balance in the organism. This has been and will remain a challenge. Understanding the different pathophysiological processes of these diseases will be the basis for predicting different clinical spectra and has the potential to offer innovative therapeutic approaches. This paper offers a practical overview of the bidirectional communication between the immune and endocrine system and the influence this has on the development of autoimmune diseases.