Neutropenia al diagnóstico de lupus eritematoso sistémico: prevalencia y correlaciones clínicas y serológicas. Nuestra cohorte / Neutropenia at diagnosis of systemic lupus erythematosus: prevalence and clinical and serological correlations. Our cohort

Introducción: las manifestaciones hematológicas en el lupus eritematoso sistémico (LES) son frecuentes. La leucopenia se presenta del 50 al 60% de los casos, pero solo el 17% tiene un recuento leucocitario <1.000/mm3. La neutropenia en pacientes con leucopenia ocurre entre un 20-40% (según el valor de corte del laboratorio). Los mecanismos posibles de neutropenia descriptos son: aumento en la destrucción de granulocitos periféricos por anticuerpos antineutrófilos, opsonización y destrucción por monocitos; cambios en el pool esplénico y marginal; y disminución en la producción medular. La formación de trampas extracelulares de neutrófilos (neutrophil extracellular traps, NETs) contribuye en la producción de interferón tipo 1 (IFN-1) a partir de plasmocitos y células dendríticas causando daño endotelial y cambios protrombóticos. La NETosis y el clearence anormal de material apoptótico promueven mayor liberación de antígenos y la consiguiente formación de autoanticuerpos. Las consecuencias infecciosas de la neutropenia al diagnóstico de LES se desconocen. Los objetivos del presente estudio fueron conocer la prevalencia de la neutropenia al diagnóstico de LES, determinar su correlación con otras variables de la patología, y estudiar su relación con una mayor probabilidad de actividad, daño, infecciones y mortalidad. Materiales y métodos: estudio descriptivo, retrospectivo. Se incluyeron pacientes con diagnóstico de LES (Systemic Lupus International Collaborating Clinics, SLICC 2012) de la cohorte del Sanatorio, desde enero de 2010 a diciembre de 2020. Se consignaron variables demográficas y asociadas a la enfermedad (criterios clínicos y de laboratorio). Escala de actividad: Systemic Lupus Erythematosus Disease Activity Index 2k (SLEDAI-2k). Se dividieron en dos grupos según la presencia de neutropenia (<1.500/mm3). Se definió un subgrupo de neutropenia severa: <500/mm3. En pacientes con neutropenia se evaluó la presencia de infección viral, bacteriana y tratamiento con factor de crecimiento de colonias de granulocitos y monocitos (GM-GSF). Análisis estadístico: los datos descriptivos se presentaron como medias y sus desvíos estándar (±DS) (variables continuas) y porcentajes (variables categóricas). Se compararon variables independientes de acuerdo con su distribución con test Mann Whitney. Se utilizó prueba t de Student para comparación de medias, y chi cuadrado (X2) para variables cualitativas. Se consideró como estadísticamente una p≤0,05. Resultados: se incluyeron 70 pacientes. Mujeres 59 (84%), edad media 38,6 años (18-72). Leucopenia 24 (34%), linfopenia 30 (42,8%), neutropenia 12 (17%), neutropenia severa 2 (2,8%) y plaquetopenia 7 (10%). Grupo con neutropenia (n=12): Sicca 12 (100%). Media índice neutrófilo/linfocito (INL) 1,33 (DS 0,69), infecciones: virus de Epstein-Barr (VEB) IgM (+) uno, parvovirus y CMV solicitados y negativos dos. PAMO realizada una: normal. Pacientes en tratamiento con GM-GSF: dos, sin eventos adversos. Dos infecciones urinarias. Conclusiones: en nuestro estudio se observó correlación entre neutropenia con síntomas Sicca, leucopenia y linfopenia, y un INL menor. Se desconoce si se relacionó a peor evolución. La presencia de infección fue baja (16%). Dos pacientes requirieron GM-GSF (con neutropenia severa), sin haber presentado eventos adversos.

Introduction: hematological manifestations are frequent in systemic erythematosus lupus (SLE). Leukopenia is seen in between 50 to 60% of cases, but only 17% has a leukocyte count <1,000/mm3. Neutropenia in patients with leukopenia occurs between 20-40% of cases, depending on the cut-off value used. Possible described mechanisms for neutropenia are: an increase in destruction of granulocytes by anti-neutrophil antibodies, opsonization and destruction by monocytes; change in the splenic and marginal neutrophil pool; a diminished production in the bone marrow. The formation of NETs contributes to the production of INF-1 from plasmocytes and dendritic cells, causing endothelial damage and pro-thrombotic changes. NETosis and apoptotic abnormal clearence promote the formation of antigens and subsequent autoantibodies. Infectious consequences of neutropenia in SLE are still unknown. The objectives of this article were to know the prevalence of neutropenia at diagnosis of SLE in our hospital, and secondly to determine its correlation with other variables of the disease and to investigate whether it's related with a greater probability of infections. Materials and methods: descriptive, retrospective study. Patients with diagnosis of SLE (SLICC 2012) from our cohort were included. Demographic and related to disease variables were stated. Activity scale: SLEDAI-2k. Patients were divided into two groups according to the presence or absence of neutropenia (<1.500/mm3 ) and multivariate analysis was performed to clinical and analytical variables. A subgroup with severe neutropenia (<500/mm3) was evaluated. Multivariate analysis was performed to detect correlations between a diminished neutrophil count and clinical manifestations, disease severity, autoantibodies profile, infections, and associated diseases. In neutropenic patients, the presence of viral or bacterial infection and the use of GM-GSF were evaluated. Statistical analysis was performed as mean +/-SD for continuous variables and percentage for categorical variables. T-Test or Mann-Whitney were used to compare independent variables according to distribution. Student's T and Chi-Square for qualitative variables. Statistical significance: p<0.05. Results: 70 patients were included. Female 59 (84%), mean age 38.6 years (18- 72). Leukopenia 24 (34%), lymphopenia 30 (42.8%), neutropenia 12 (17%), severe 2 (2.8%), thrombocytopenia 7 (10%). Neutropenic group: Sicca 12 (100%), neutrophil/lymphocyte index (NLI) 1.33 (DS 0.69), infections: EBV IgM+1/12, parvovirus and CMV negative 2/12. BMA 1/12, without pathologic findings. GM-GSF 2/12. Infections: 2/12 (urinary). Conclusions: we observed a correlation between Sicca symptoms, leuko and lymphopenia, and a lower NLI. The clinical significance of these findings was uncertain. The presence of infection was low (16%). Two required GM-GSF, having not presented adverse events.

Plasmaféresis en lupus eritematoso sistémico neuropsiquiátrico

De las complicaciones sistémicas más temidas del lupus eritematoso sistémico, destaca el compromiso neuropsiquiátrico y en especial la psicosis asociada. A pesar del gran espectro de presentaciones clínicas y ambigua definición, la sospecha clínica y el registro de casos ha ido en aumento en los últimos años. Poca evidencia científica existe sobre el tratamiento de la psicosis asociada al lupus eritematoso sistémico; sin embargo, se reconoce como un fenómeno autoinmune mediado por anticuerpos, sin que exista daño estructural cerebral. Los esteroides, ciclofosfamida y rituximab forman parte de las opciones terapéuticas. Se presenta el caso de una adolescente de 13 años, con diagnóstico reciente de lupus eritematoso sistémico y en quien una de las principales manifestaciones iniciales fue afección neuropsiquiátrica, en especial psicosis refractaria. Los tratamientos con glucocorticoides y ciclofosfamida fueron inefectivos y se logró remisión exitosa únicamente con el uso de plasmaféresis terapéutica. En total, se ofrecieron 4 sesiones de plasmaféresis con albúmina humana, logrando rápida remisión de su psicosis.

One of the most feared clinical presentations of systemic lupus erythematosus is neuropsychiatric involvement, specially associated psychosis. Diagnostic definitions are not well stablished to date however clinical suspicion and case registry has been increasing over time. There is scarce evidence regarding correct therapeutic approach to psychiatric presentations of systemic lupus erythematosus, however, it is well known that it is consequence of noxious autoimmune activity of the brain without structural compromise. Corticosteroids, cyclophosphamide and rituximab are part of the pharmacologic tools available. We present a case a 13 year old adolescent with new onset systemic lupus erythematosus in whom one of the principal initial concerns was how to address intense neuropsychiatric manifestations and specially refractory psychosis. First, high doses of steroid boluses were offered with no benefit in psychiatric symptoms, then cyclophosphamide was administered, with no success. Finally, therapeutic plasma exchange was offered to the patient with rapid clinical improvement. A total of 4 sessions of plasmapheresis with human albumin were done.

Infección por Listeria monocytogenes en una mujer gestante con lupus eritematoso sistémico y síndrome HELLP / Listeria monocytogenes infection in a pregnant woman with systemic lupus erythematosus and HELLP syndrome / Infeção por Listeria monocytogenes em uma mulher gestante com antecedente de lúpus eritromatoso sistemático e síndrome HELLP

La listeriosis es una enfermedad transmitida principalmente por alimentos contaminados con Listeria monocytogenes. Se presenta con mayor frecuencia en neonatos, mayores de 65 años, mujeres gestantes y pacientes inmunosuprimidos. La infección por L. monocytogenes durante la gestación se asocia a una importante morbimortalidad materno-fetal.Se reporta el caso de una mujer gestante de 29 años de edad con lupus eritematoso sistémico, a quien se le diagnosticó bacteriemia por L. monocytogenes. Durante la hospitalización, el cuadro clínico se complicó con hipertransaminasemia y, ante la presencia de trombocitopenia, se estableció el diagnóstico presuntivo de síndrome HELLP. El alto riesgo de morbimortalidad llevó a una finalización precoz de la gestación.La importancia de este trabajo clínico radica en presentar la dificultad en el diagnóstico y manejo en una paciente gestante de gran complejidad con una infección relativamente frecuente que puede pasar desapercibida.

Listeriosis is a disease mainly transmitted by food contaminated with bacteria called Listeria monocytogenes. It occurs more often in newborns, elder population, pregnant women and immunosuppressed patients. L. monocytogenes infection during pregnancy is associated to significant maternal mortality and morbidity. The case of a 29-year-old pregnant woman with history of Systemic Lupus Erythematosus is review. The said woman was diagnosed with bacteremia related to L. monocytogenes. During hospitalization, the patient experienced complications with hipertransaminasemia, which led to the presumptive diagnosis of HELLP in presence of thrombocytopenia. Given the high risk of mortality and morbidity, the pregnancy was terminated. The importance of the present clinical work lays in showing the difficulties embedded in diagnosing and handling a high-complexity pregnant patient presenting a frequent infection that would otherwise go undetected.

A listeriosis é uma doença transmitida principalmente por alimentos contaminados com Listeria monocytogenes. Apresentase com maior frequência em neonatos, maiores de 65 anos, mulheres gestantes e pacientes imunossuprimidos. Durante a gestação esta infeção associa-se a uma importante morbimortalidade materno-fetal. Foi reportado o caso de uma mulher gestante de 29 anos com antecedente de lúpus eritematoso sistémico, diagnosticada com bacteriemia por L. monocytogenes, na hospitalização teve complicações com hipertransaminasemia, foi estabelecido um diagnostico presuntivo de síndrome HELLP em presença de trombocitopenia. O alto risco de morbimortalidade levou a uma finalização precoce da gestação. A importância deste trabalho clínico radica em apresentar a dificuldade de diagnóstico e tratamento em pacientes gestantes de alta complexidade com infeção relativamente frequente, que pode passar desapercebida

Diagnóstico simultâneo de lúpus eritematoso sistêmico e chikungunya / Simultaneous diagnosis of systemic erythematosus lupus and chikungunya

Chikungunya é uma arbovirose caracterizada por febre alta, poliartralgia periférica, exantema, mialgia axial e intensa fadiga. Até 65% dos pacientes apresentam recuperação total dos sintomas em 4 semanas, contudo as dores articulares podem persistir por um período de 12 meses após a infecção em 4,1% dos pacientes e por até dois anos em 1,6% dos indivíduos acometidos. Um ano após a infecção 0,3% dos pacientes podem apresentar artrite inflamatória crônica. Os pacientes que permanecem com dores musculoesqueléticas e artrite pós-infecciosa são frequentemente tratados com drogas imunossupressoras. Por poderem apresentar quadro clínico semelhante e pelo fato de infecção ser comum nos pacientes portadores de doenças reumatológicas, o lúpus eritematoso sistêmico (LES) é uma afecção que deve ser abordada como diagnóstico diferencial em regiões endêmicas para essa arbovirose. Sabendo-se do crescente número de casos de chikungunya no Brasil e da relação fortemente estabelecida entre aumento de morbimortalidade em lúpicos nos quadros infecciosos, faz- se necessária uma ampla discussão dos casos emergentes. (AU)

Chikungunya is an arbovirose characterized by high fever, severe peripheral polyarthralgia, exanthema, axial myalgia and intense fatigue. Up to 65% of patients present complete recovery of symptoms at 4 weeks, however, joint pain may persist for a period of 12 months after infection in 4.1% of patients and for up to 2 years in 1.6% of affected individuals. One year after infection, 0.3% of patients may present with chronic inflammatory arthritis. Patients who remain with musculoskeletal pain and post-infectious arthritis are often treated with Immunosuppressive drugs. Due to the presence of similar clinics and the fact that double infection is common in patients with rheumatologic diseases in some populations, systemic lupus erythematosus (SLE) is a condition that must be addressed during the stipulation of differential diagnosis in regions endemic to arboviruses. Given the increasing number of cases of chikungunya in developing countries and the strongly established relationship between increased morbidity and mortality in lupus in infectious diseases, a broad discussion of emerging cases is required. (AU)

Mortality from systemic erythematosus lupus in Brazil: evaluation of causes according to the government health database / Mortalidade por lúpus eritematoso sistêmico no Brasil: avaliação das causas de acordo com o banco de dados de saúde do governo

Abstract Objective: To characterize the causes of mortality in patients with systemic lupus erythematosus (SLE) in Brazil between 2002 and 2011. Methods: An exploratory ecological study of a time series using data from the Mortality Information System of DATASUS, the Department of the Unified Health System (Brazil's National Health System). Results: Brazil's SLE mortality rate was 4.76 deaths/105 inhabitants. The mortality rate was higher in the Midwest, North and Southeast regions than in the country as a whole. There were 6.3% fewer and 4.2% more deaths than expected in the Northeast and Southeast regions, respectively. The mean age at death was 40.7 ± 18 years, and 45.61% of deaths occurred between the ages of 20 and 39. Incidence was highest in women (90.7%) and whites (49.2%). Disorders of the musculoskeletal system and connective tissue were mentioned as an underlying cause of death in 77.5% of cases, and diseases of the circulatory system and infectious and parasitic diseases were also noted in fewer cases. SLE was mentioned as an underlying cause of death in 77% of cases, with no difference between the Brazilian regions (p = 0.2058). The main SLE-related causes of death were, sequentially, diseases of the respiratory and circulatory systems and infectious and parasitic diseases. Conclusions: This study identified a need for greater control of risk factors for cardiovascular diseases and a better understanding of the pathogenesis of atherosclerosis in SLE. Infectious causes are still frequent, and management should be improved, especially in the early stages of the disease.

Resumo Objetivo: Caracterizar as causas de mortalidade em pacientes com lúpus eritematoso sistêmico (LES) no Brasil entre 2002 e 2011. Métodos: Estudo ecológico exploratório de uma série cronológica com dados do Sistema de Informações sobre Mortalidade do Departamento de Informática do Sistema Único de Saúde (Datasus). Resultados: A taxa de mortalidade por LES no Brasil foi de 4,76 mortes/105 habitantes. A taxa de mortalidade foi maior nas regiões Centro-Oeste, Norte e Sudeste do que no país como um todo. Houve 6,3% menos e 4,2% mais mortes do que o esperado nas regiões Nordeste e Sudeste, respectivamente. A média de idade ao óbito foi de 40,7 ± 18 anos e 45,61% dos óbitos ocorreram entre 20 e 39 anos. A incidência foi maior nas mulheres (90,7%) e nos brancos (49,2%). Os distúrbios do sistema musculoesquelético e do tecido conjuntivo foram mencionados como a causa subjacente de morte em 77,5% dos casos; também foram observadas doenças do sistema circulatório e infecciosas e parasitárias, embora em menor frequência. O LES foi mencionado como a causa subjacente de óbito em 77% dos casos, sem diferença entre as regiões brasileiras (p = 0,2058). As principais causas de morte associadas ao LES foram, em ordem, doenças dos sistemas respiratório e circulatório e doenças infecciosas e parasitárias. Conclusões: Este estudo identificou a necessidade de maior controle dos fatores de risco para doenças cardiovasculares e uma melhor compreensão da patogênese da aterosclerose no LES. As causas infecciosas ainda são frequentes e o manejo deve ser melhorado, especialmente nos estágios iniciais da doença.

Chronic low back pain in patients with systemic lupus erythematosus: prevalence and predictors of back muscle strength and its correlation with disability / Lombalgia crônica em pacientes com lúpus eritematoso sistêmico: prevalência e preditores da força muscular de extensão de tronco e sua correlação com a incapacidade

Abstract Objective: To determine the prevalence of Chronic Low Back Pain and predictors of Back Muscle Strength in patients with Systemic Lupus Erythematosus. Methods: Cross-sectional study. Ninety-six ambulatory patients with lupus were selected by non-probability sampling and interviewed and tested during medical consultation. The outcomes measurements were: Point prevalence of chronic low back pain, Oswestry Disability Index, Tampa Scale of Kinesiophobia, Fatigue Severity Scale and maximal voluntary isometric contractions of handgrip and of the back muscles. Correlation coefficient and multiple linear regression were used in statistical analysis. Results: Of the 96 individuals interviewed, 25 had chronic low back pain, indicating a point prevalence of 26% (92% women). The correlation between the Oswestry Index and maximal voluntary isometric contraction of the back muscles was r = −0.4, 95% CI [−0.68; −0.01] and between the maximal voluntary isometric contraction of handgrip and of the back muscles was r = 0.72, 95% CI [0.51; 0.88]. The regression model presented the highest value of R 2 being observed when maximal voluntary isometric contraction of the back muscles was tested with five independent variables (63%). In this model handgrip strength was the only predictive variable (β = 0.61, p = 0.001). Conclusions: The prevalence of chronic low back pain in individuals with systemic lupus erythematosus was 26%. The maximal voluntary isometric contraction of the back muscles was 63% predicted by five variables of interest, however, only the handgrip strength was a statistically significant predictive variable. The maximal voluntary isometric contraction of the back muscles presented a linear relation directly proportional to handgrip and inversely proportional to Oswestry Index i.e. stronger back muscles are associated with lower disability scores.

Resumo Objetivo: Determinar a prevalência de lombalgia crônica (LBC) e os preditores de força muscular nas costas (FMC) em pacientes com lúpus eritematoso sistêmico (LES). Métodos: Estudo transversal. Selecionaram-se 96 pacientes ambulatoriais com LES por amostragem não probabilística, entrevistados e testados durante consultas médicas. As medidas de desfecho foram: prevalência ocasional de LBC, Índice de Incapacidade de Oswestry, Escala Tampa para Cinesiofobia, Escala de Gravidade da Fadiga e contrações isométricas voluntárias máximas (CIVM) de preensão manual e dos músculos das costas. Usaram-se o coeficiente de correlação e a regressão linear múltipla na análise estatística. Resultados: Dos 96 indivíduos entrevistados, 25 apresentavam LBC, o que indicou uma prevalência circunstancial de 26% (92% mulheres). A correlação entre o Índice de Incapacidade de Oswestry e a contração isométrica voluntária máxima dos músculos das costas foi de r = -0,4, IC 95% [-0,68; -0,01] e entre a CIVM de preensão manual e dos músculos das costas foi de r = 0,72, IC 95% [0,51; 0,88]. O modelo de regressão apresentou o maior valor de R2 observado quando a CIVM dos músculos das costas foi testada com cinco variáveis independentes (63%). Nesse modelo, a força de preensão manual foi a única variável preditiva (ß = 0,61, p = 0,001). Conclusões: A prevalência de LBC em indivíduos com LES foi de 26%. A CIVM dos músculos das costas foi 63% prevista por cinco variáveis de interesse. No entanto, apenas a força de preensão manual foi uma variável preditiva estatisticamente significativa. A CIVM dos músculos das costas apresentou uma relação linear diretamente proporcional à força de preensão manual e inversamente proporcional ao Índice de Incapacidade de Oswestry (ou seja, músculos das costas mais fortes estão associados a menores pontuações de incapacidade).

Lupus palpebral: a propósito de dos casos / Palpebral lupus: apropos of two cases

El lupus eritematoso es una dermatosis inflamatoria, crónica, aguda o subaguda que evoluciona por brotes. Puede afectar a todos los órganos pero más frecuentemente a la piel. Presentamos a dos pacientes con lesión en forma de placa, localizada en zona interna y media del borde libre palpebral inferior, de bordes elevados, depresión central con fondo costroso y pérdida de las pestañas a ese nivel. Se decide -por la localización, extensión de la lesión, los antecedentes personales y la aplicación de tratamientos previos sin mejoría del cuadro clínico- realizar biopsia incisional para un mejor estudio. Los resultados anatomopatológicos revelaron el diagnóstico de lupus discoide palpebral. La evolución posterior al tratamiento médico fue satisfactoria, sin recidiva de la lesión durante el primer año de seguimiento.

Erythematosus lupus is an inflammatory dermatosis of chronic, acute or subacute nature that occurs in outbreaks. It can affect all the body organs, but mainly the skin. Here are two patients with plaque-form lesions located in the internal middle area of the free inferior palpebral border, thick contours, central depression with scabby bottom and loss of eyelash. Taking into account the location, the extension of the lesion, personal histories and application of previous treatment without improved clinical picture, it was decided to perform incisional biopsy for better examination. The anatomopathological results showed the diagnosis of palpebral discoid lupus. The recovery of the patient was satisfactory after the medical treatment, with no relapse during the first follow-up year.

Influence of gonadal hormones on the proliferation of lymphocytes in systemic lupus erythematosus (SLE) patients and the related mechanism / 中国免疫学杂志

Objective:To study the influence of gonadal hormones on the function of lymphocytes of SLE patients through detecting the expression of estrogen receptor alpha(ER?) and the function of peripheral blood lymphocytes of SLE patients.Methods:Blood samples of 33 SLE patients and 31 normal controls were collected.Estradiol(E2) and testosterone (T) concentration in peripheral blood were detected by ELISA,the proliferating reaction of T lymphocyte stimulated by ConA were detected by methyl thiazolyl tetrazolium (MTT) assay and the expression of estrogen receptor alpha(ER?)mRNA of peripheral blood mononuclear cells (PBMCs),T lymphocytes and B lymphocytes were detected by RT-PCR.Results:Compared with normal control,the stimulating index of T lymphocyte proliferation decreased(P