Disfunción sexual en mujeres con lupus eritematoso sistémico / Sexual dysfunction in women with systemic lupus erythematosus

Introducción: la disfunción sexual (DS) es la alteración en una o varias de las fases de la actividad sexual. Puede culminar en frustración, dolor y disminución de la frecuencia de las relaciones sexuales. Objetivos: determinar la frecuencia de DS y analizar los factores asociados en pacientes con lupus eritematoso sistémico (LES). Materiales y métodos: se realizó un estudio de corte transversal. Se incluyeron pacientes femeninas con LES, entre 18 y 50 años, se excluyeron aquellas con síndrome de Sjögren, menopausia, depresión severa y analfabetas. Se evaluaron variables demográficas y de la enfermedad. Se aplicó la escala Depression Anxiety Stress Scale (DASS-21) y el Índice de Función Sexual Femenina (Female Sexual Function Index, FSFI). Se comparó con un grupo control sano. Resultados: se evaluaron 60 mujeres con LES y 63 controles. La prevalencia de DS en LES fue de 71,7% y hubo diferencias significativas en todos los dominios de la función sexual. El score total del FSFI en pacientes con LES fue menor al comparar con los controles. Según la escala DASS-21, estrés, ansiedad y depresión se observaron en al menos la mitad de mujeres lúpicas, sin embargo, no se encontró asociación entre estas variables y DS. Conclusiones: la prevalencia de DS en pacientes con LES fue elevada. Depresión, ansiedad y estrés no fueron determinantes en la presencia de DS.

Introduction: sexual dysfunction is the alteration in one or several phases of sexual activity. It can culminate in frustration, pain and a decrease in the frequency of sexual intercourse. Objectives: determine the frequency of sexual dysfunction and analyze associated factors in patients with SLE. Materials and methods: a descriptive cross-sectional study was conducted. We included patients with SLE, between 18 and 50 years of age, Secondary Sjogren's syndrome, menopause, severe depression and illiterate patients were excluded. Demographic and disease-related variables were studied. The Depression Anxiety Stress Scale (DASS-21), and the Female Sexual Function Index (FSFI) were applied. Results: sixty women with SLE and 63 controls were evaluated. The prevalence of SD in SLE was 71.7% and there were significant differences in all domains of sexual function. The total FSFI score in patients with SLE was lower when compared to controls. According to the DASS-21 scale, stress, anxiety and depression were observed in at least half of lupus women, however no association was found between these variables and SD. Conclusions: the prevalence of SD in patients with SLE was high. Depression, Anxiety, and Stress were not determinants in the presence of SD.

Neurofuncionalidad de los procesos de memoria y funciones ejecutivas en pacientes con lupus eritematoso sistémico / Neurofunctionality of memory and executive functions processes in patients with systemic lupus erythematosus / Neurofuncionalidade dos processos de memória e funções executivas em pacientes com lúpus eritematoso sistêmico

Esta investigación se propuso determinar el funcionamiento neuropsicológico de los procesos de memoria y funciones ejecutivas en el lupus eritematoso sistémico (LES). Se planteó como un estudio con enfoque cuantitativo, de diseño comparativo-correlacional y siguiendo un modelo no probabilístico para la selección de la muestra. Participaron 68 personas divididas en dos grupos equitativos, homólogos en edad, género y nivel de escolaridad. Se emplearon escalas para la medición de la funcionalidad en actividades cotidianas, y test estandarizados para la medición de los procesos de memoria y funciones ejecutivas. Se encontró que, el LES afecta la memoria verbal para información con contexto, tanto en almacenes de corto como de largo plazo, y la memoria visual a largo plazo; los pacientes presentan mayores fenómenos patológicos asociados a intrusiones y perseveraciones, y afecta el reconocimiento de la información; también altera la regulación conductual y la velocidad de procesamiento de la información, entre otras capacidades cognitivas, destacándose la tendencia al pensamiento concreto. Logró determinarse que el LES dificulta el funcionamiento de estos procesos cognitivos de forma diversa en sus diferentes formas de actividad funcional, siendo susceptible de modificar su influencia al considerarse factores como la edad, el tiempo en que tarda en establecerse el diagnóstico y el tiempo en tratamiento.

This research aimed to determine the neuropsychological functioning of memory and executive functions processes in systemic lupus erythematosus (SLE). It was proposed as a study with a quantitative approach, comparative-correlational design followed by a non-probabilistic model for sample selection. 68 participants were divided into two equitable groups, peers in age, gender and level of education. Scales were used to measure functionality in daily activities, and standardized tests for the measurement of memory and executive functions processes. It was found that SLE affects verbal memory for information with context in both short and long-term stores and long-term visual memory, patients present greater pathological phenomena associated with intrusions and perseverations and affects the recognition of information; it also alters the behavioral regulation and the speed of information processing, among other cognitive abilities, highlighting the tendency to concrete thinking. It was determined that SLE hinders the functioning of these cognitive processes in different ways and different forms of functional activity, being able to modify their influence by considering factors such as age, time it takes to establish the diagnosis and time in treatment.

Esta pesquisa teve como objetivo determinar o funcionamento neuropsicológico dos processos de memória e funções executivas nos lúpus eritematoso sistêmico (LES). Para isso, foi proposto um estudo com abordagem quantitativa, design comparativo-correlacional e seguindo um modelo não probabilístico para a seleção da amostra. Participaram 68 pessoas que foram divididas em dois grupos equitativos, pares em idade, gênero e nível de educação. Foram usadas escalas para medir a funcionalidade em atividades diárias, bem como testes padronizados para a medição de processos de memória e funções executivas. Verificou-se que o LES afeta a memória verbal para informações com contexto em armazenes de curto e longo prazo e em memória visual de longo prazo; os pacientes apresentam mais fenômenos patológicos associados às intrusões e perseverações, e afeta o reconhecimento da informação; altera também a regulação comportamental e a velocidade do processamento da informação, entre outras habilidades cognitivas, destacando a tendência ao pensamento concreto. Assim, determinou-se que o LES dificulta o funcionamento desses processos cognitivos de diferentes formas de atividade funcional, sendo suscetível de modificar sua influência quando são considerados fatores como a idade, o tempo em que tardou para estabelecer-se o diagnóstico e o tempo sob tratamento.

Neuropsychiatric lupus erythematosus: future directions and challenges; a systematic review and survey

This study aimed to systematically review neuropsychiatric lupus erythematosus (NPSLE) and establish a simplified diagnostic criterion for NPSLE. Publications from 1994 to 2018 in the database (Wanfang data (http://www.wanfangdata.com.cn/index.html) and China National Knowledge Internet (http://www.cnki.net)) were included. In total, 284 original case reports and 24 unpublished cases were collected, and clinical parameters were analyzed. An attempt was made to develop a set of simplified diagnostic criteria for NPSLE based on cases described in the survey and literature; moreover, and pathophysiology and management guidelines were studied. The incidence rate of NPSLE was estimated to be 12.4% of SLE patients in China. A total of 408 NPSLE patients had 652 NP events, of which 91.2% affected the central nervous system and 8.8% affected the peripheral nervous system. Five signs (manifestations, disease activity, antibodies, thrombosis, and skin lesions) showed that negative and positive predictive values were more than 70%, included in the diagnostic criteria. The specificity, accuracy, and positive predictive value (PPV) of the revised diagnostic criteria were significantly higher than those of the American College of Rheumatology (ACR) criteria (χ2=13.642, 15.591, 65.010, p<0.001). The area under the curve (AUC) for revised diagnostic criteria was 0.962 (standard error=0.015, 95% confidence intervals [CI] =0.933-0.990), while the AUC for the ACR criteria was 0.900 (standard error=0.024, 95% CI=0.853-0.946). The AUC for the revised diagnostic criteria was different from that for the ACR criteria (Z=2.19, p<0.05). Understanding the pathophysiologic mechanisms leading to NPSLE is essential for the evaluation and design of effective interventions. The set of diagnostic criteria proposed here represents a simplified, reliable, and cost-effective approach used to diagnose NPSLE. The revised diagnostic criteria may improve the accuracy rate for diagnosing NPSLE compared to the ACR criteria.

Small fiber neuropathy and related factors in patients with systemic lupus erythematosus; the results of cutaneous silent period and skin biopsy

Abstract Introduction Evaluating small nerve fibers in patients with systemic lupus erythematosus (SLE) using cutaneous silent period (CSP) and skin biopsy and assesssing the relationship between clinical signs, autoantibodies and neuropathic pain score. Objective - methods Fifty one SLE patients and 46 healthy volunteers were included in this study. Nerve conduction studies and CSP were performed both on upper and lower limbs in subjects. Skin biopsy was performed and the number of epidermal nerve density and IL-6 staining were evaluated. Results In SLE patients, CSP latencies were significantly prolonged both in lower and upper limbs and lower and upper extremity CSP durations were significantly shorter when compared to controls ( p < 0.001). The number of epidermal nerve was significantly lower in SLE patients when compared to healthy controls ( p < 0.001). Conclusion We detected marked small nerve fiber damage in both lower and upper limbs in SLE patients using CSP. Decreased epidermal nerve density also supports this finding.(AU)

Active human herpesvirus infections in adults with systemic lupus erythematosus and correlation with the SLEDAI score

Abstract Background: Human herpesviruses (HHVs) are responsible for a significant number of clinical manifestations in systemic lupus erythematous (SLE) patients. The aim of this study was to determine the frequency of active HHV infections in SLE patients and correlating them with disease activity. Methods: Serum samples were collected from 71 SLE patients and their DNAs were extracted and analyzed to detect HHV-DNA viruses using the nucleic acid amplification technique. Results: Fifteen out of the 71 (21.1%) patients tested positive for the HHV-DNA virus. Of them, 11/15 HHV-DNA-positive patients (73.3%) had SLE activity index (SLEDAI - Systemic Lupus Erythematosus Disease Activity Index) ≥8 (p = 0.0001). Active HCMV infection was the mostly frequently observed infection, occurring in 6/15 patients (40%). The frequencies of other active viral infections were 22% for HSV-1, 16.7% for HHV-7, and 5.5% for HSV-2. Viral coinfection (two or more viruses detected in the same sample) occurred in three patients (16.7%). Active HHV infections in SLE patients are more frequent in those with active SLE (≥8), who is at high risk of HHV reactivation and HCMV disease. Conclusion: Viral surveillance is important to identify active HHV infections that can cause clinical symptoms and other complication in SLE patients.

Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onsetlupus nephritis

Abstract Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study. Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN. Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02). Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.(AU)

Comparison of lupus patients with early and late onset nephritis: a study in 71 patients from a single referral center

Abstract Background: Nephritis occurs frequently in systemic lupus erythematosus (SLE) and may worsen disease morbidity and mortality. Knowing all characteristics of this manifestation helps to a prompt recognition and treatment. Aim: To compare the differences in clinical data, serological profile and treatment response of nephritis of early and late onset. Methods: Retrospective study of 71 SLE patients with biopsy proven nephritis divided in early nephritis group (diagnosis of nephritis in the first 5 years of the disease) and late nephritis (diagnosis of nephritis after 5 years). Epidemiological, serological, clinical and treatment data were collected from charts and compared. Results: In this sample, 70. 4% had early onset nephritis and 29.6% had late onset. No differences were noted in epidemiological, clinical, serological profile, SLICC and SLEDAI, except that late onset nephritis patients were older at nephritis diagnosis (p = 0.01). Regarding renal biopsy classification, C3 and C4 levels, serum creatinine, 24 h proteinuria and response rate to treatment the two groups were similar (p = NS). Patients with early onset had lower levels of hemoglobin at nephritis onset than those of late onset (p = 0.02). Conclusions: Most of SLE patients had nephritis in the first 5 years of disease. No major differences were noted when disease profile or treatment outcome of early and late onset nephritis were compared.(AU)

Células T reguladoras en lupus eritematoso generalizado / Regulatory T cells in systemic lupus erythematosus

Resumen El lupus eritematoso generalizado (LEG) es una enfermedad autoinmune crónica caracterizada por la pérdida de la tolerancia a los antígenos propios y la síntesis de diferentes autoanticuerpos con la formación y depósito de complejos inmunes y el daño de múltiples órganos. Las células T reguladoras (Treg) desempeñan un papel esencial en el mantenimiento de la tolerancia periférica, controlan el estado de activación del sistema inmune y limitan las respuestas autoinmunes. El estudio del número y la función de las diferentes subpoblaciones de células Treg en LEG ha sido objeto de una intensa investigación. Dependiendo del fenotipo de las células Treg analizado se ha reportado que la frecuencia de estas células en pacientes con LEG se encuentra disminuida, aumentada o sin alteraciones. Además, diferentes grupos han descrito que la función supresora de las células Treg de los pacientes con LEG se encuentra reducida o no se ve afectada. En conjunto, lo datos reportados sugieren que las células Treg desempeñan un papel relevante en la patogénesis del LEG y que estos linfocitos pueden ser considerados blancos potenciales para el diseño de nuevas estrategias terapéuticas para esta enfermedad.

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a loss of tolerance to self-antigens and synthesis of different autoantibodies, with the formation and deposition of immune complexes and damage to multiple organs. T regulatory cells (Tregs) play a crucial role in maintaining peripheral tolerance, controlling the state of activation of the immune system and limiting autoimmune responses. The study of the number and function of the different Treg cell subpopulations in SLE has been the subject of intense research. Depending on the analyzed Treg cell phenotype, the frequency of these cells has been reported to be reduced, increased or unaltered in patients with SLE. In addition, different groups have described that Treg cells suppressive function is reduced or unaffected in patients with SLE. Taken together, the reported data suggest that Treg cells play a relevant role in the pathogenesis of SLE and that these lymphocytes can be considered potential targets for the design of new therapeutic strategies for this condition.

Relación entre los factores sociodemográficos y la calidad de vida en pacientes con lupus eritematoso sistémico / Relationship between sociodemographic factors and the quality of life in patients with systemic lupus erythematosus

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que puede tener repercusiones negativas en la calidad de vida (CV) de quienes la padecen. La CV puede verse influida por factores sociodemográficos (FSD) relacionados con la enfermedad en sí. Objetivo: Determinar la relación entre los FSD y la CV en pacientes con LES. Métodos: Estudio descriptivo, de corte transversal, de campo y observacional, donde se evaluaron 100 pacientes con diagnóstico de LES. Se emplearon dos encuestas: una para la recolección de datos sociodemográficos y el formulario de la Escala GENCAT. Resultados: La edad promedio fue 42,9 años ± 13,5, el sexo más afectado fue femenino con 93%, los años de estudio promedio fueron 11,4 años ± 4,4 y el tiempo de evolución del LES promedio fue 11,1 años ± 9,5. La CV según el formulario de la Escala GENCAT fue aceptable; la edad avanzada y mayor tiempo de evolución de LES se asoció con menor CV, y mayor escolaridad se asoció con mayor CV. Conclusiones: La CV fue aceptable según la Escala GENCAT, y se encontraron asociaciones entre la CV y edad, años de estudio y tiempo de evolución del LES que fueron estadísticamente significativas(AU)

Systemic lupus erythematosus (SLE) is an autoimmune disease that can have a negative impact on the quality of life (QoL) of those who suffer from it. QoL may be influenced by sociodemographic factors (SDF) related to the disease itself. Objective: Determine the relationship between the SDF and the QoL in patients with SLE. Methods: Descriptive, cross-sectional, field and observational study, where 100 patients with a diagnosis of SLE were evaluated. Two surveys were used: one for the collection of sociodemographic data and the GENCAT Scale form. Results: The average age was 42.9 years ± 13.5, the most affected sex was female with 93%, the average study years were 11.4 years ± 4.4 and the evolution time of the average SLE was 11.1 year ± 9.5. TheQoL according to the GENCAT Scale form was acceptable; the advanced age and longer time of evolution of SLE was associated with lower QoL, and higher schooling was associated with higher QoL. Conclusions: The QoL was acceptable according to the GENCAT Scale, and associations were found between the QoL and age, years of study and time of evolution of the disease, which were statistically significant(AU)

Nailfold capillaroscopy as a risk factor for pulmonary arterial hypertension in systemic lupus erythematosus patients

Abstract Background: Pulmonary arterial hypertension (PAH) is a rare and severe complication of systemic lupus erythematosus (SLE). This study aimed to evaluate clinical and laboratory risk factors associated with PAH in SLE patients. Methods: This was a retrospective case-control study in which patients with SLE with PAH (SLE-PAH) confirmed by right heart catheterization (RHC) were compared with SLE patients without PAH. Clinical and demographic variables related to SLE and PAH and nailfold capillaroscopy were evaluated by reviewing the medical records of the patients. Results: Twenty-one patients with SLE-PAH and 44 patients with SLE without PAH matched for sex and disease duration were included. The scleroderma (SD) pattern on nailfold capillaroscopy was more frequently found in patients with SLE-PAH than in those without PAH (56.3% versus 15.9%, respectively, p = 0.002). By univariate analysis, Raynaud's phenomenon, history of abortion, and SD pattern on capillaroscopy were associated with PAH. Arthritis was a protective factor for PAH development. Multivariate analysis showed that the SD pattern on capillaroscopy was the only variable associated with a significantly higher risk of PAH, with an odds ratio of 6.393 (95% confidence interval, 1.530-26.716; p = 0.011). Conclusion: In this study, SD pattern was associated with a 6.3-fold increased risk for PAH development in SLE patients, suggesting that nailfold capillaroscopy might be useful as a screening method to identify SLE patients with a high risk of developing this severe complication.

Early Assessment of Right Ventricular Function in Systemic Lupus Erythematosus Patients using Strain and Strain Rate Imaging / Avaliação Precoce da Função Ventricular Direita em Pacientes com Lúpus Eritematoso Sistêmico pelo Strain e Strain Rate

Abstract Background: Right ventricular function is a crucial factor of the prognosis of systemic lupus erythematosus (SLE). Objectives: To evaluate the right ventricular function in SLE patients with different degrees of pulmonary hypertension (PH) by strain and strain rate imaging. Methods: A total of 102 SLE patients and 30 healthy volunteers were studied between October 2015 and May 2016. Patients were divided into three groups according to pulmonary artery systolic pressure (PASP) estimated by echocardiography: group control (A); PASP ≤ 30 mmHg (group B, n = 37); PASP 30-50 mmHg (mild PH; group C, n = 34); and PASP ≥ 50 mmHg (moderate-to-severe PH; group D, n = 31). Longitudinal peak systolic strain (ε) and strain rate (SR), including systolic strain rate (SRs), early diastolic strain rate (SRe) and late diastolic strain rate (SRa) were measured in the basal, middle and apical segments of the right ventricular free wall in participants by two-dimensional speckle tracking echocardiography (2D-STE) from the apical four-chamber view. A p < 0.05 was set for statistical significance. Results: The parameters of ε, SRs, SRe, and SRa were significantly decreased in groups C and D compared with groups A and B. The ε of each segments was significantly lower in group D than in group C, while there were no differences in SRs, SRe and SRa between groups C and D. Conclusions: Strain and strain rate imaging could early detect the right ventricular dysfunction in SLE patients with PH, and provide important value for clinical therapy and prognosis of these patients. (Arq Bras Cardiol. 2018; [online].ahead print, PP.0-0)

Resumo Fundamento: A função ventricular direita é fator crucial do prognóstico do lúpus eritematoso sistêmico (LES). Objetivos: Avaliar a função ventricular direita em pacientes com LES e diferentes graus de hipertensão pulmonar (HP) por avaliação do strain e do strain rate. Métodos: Um total de 102 pacientes com LES e 30 voluntários sadios foram estudados entre outubro de 2015 e maio de 2016. Os pacientes foram divididos em três grupos de acordo com a pressão sistólica da artéria pulmonar (PSAP) estimada por ecocardiografia: grupo controle (A); PSAP ≤ 30 mmHg (grupo B, n = 37); PSAP 30-50 mmHg (HP leve; grupo C, n = 34); e PSAP ≥ 50 mmHg (HP moderada a grave; grupo D, n = 31). Foram medidos, nos segmentos basal, medial e apical da parede livre do ventrículo direito, o pico sistólico longitudinal (ε) e o strain rate (SR), incluindo o SR sistólico (SRs), o SR diastólico precoce (SRp) e o SR diastólico tardio (SRt) pela técnica de ecocardiografia bidimensional com rastreamento de "pontos" (two-dimensional speckle tracking echocardiography, 2D-STE) pela visualização apical de quatro câmaras. Um p < 0,05 foi adotado como estatisticamente significativo. Resultados: Os parâmetros ε, SRs, SRp e SRt foram significativamente menores nos grupos C e D em comparação aos grupos A e B. O ε de cada segmento foi significativamente menor no grupo D que no grupo C, ao passo que não houve diferença no SRs, SRp ou SRt entre os grupos C e D. Conclusões: O strain e o SR obtidos por 2D-STE puderam detectar precocemente disfunção ventricular direita em pacientes com LES e HP, contribuindo para o tratamento clínico e prognóstico desses pacientes. (Arq Bras Cardiol. 2018; [online].ahead print, PP.0-0)

Study of bone mineral density and serum bone turnover markers in newly diagnosed systemic lupus erythematosus patients / 北京大学学报(医学版)

OBJECTIVE@#To investigate the changes of bone mineral density (BMD) and serum bone turnover factor in newly diagnosed systemic lupus erythematous (SLE) patients.@*METHODS@#Eighty newly diagnosed SLE patients and 80 age and gender matched healthy controls were enrolled. None of the SLE patients had ever received glucocorticoid, immunosuppressive agents or vitamin D. BMD was measured at radius,lumbar spine and hip by dual X ray absorptiometry (DXA). Bone turnover markers including serum levels of tartrate-resistant acid phosphatase 5b (TRAP5b),bone alkaline phosphatase (BAP) and 25-hydroxy vitamin D3 (25-OH-VD3) were measured by enzyme-linked immunosorbent assay (ELISA). Logistic regression was employed to analyze the risk factors associated with decreased BMD.@*RESULTS@#Mean age of the SLE patients was (32.8±12.4) years, and 85% were female, none of whom were post-menopausal. BMD was significantly reduced in all the measured sites, compared with the healthy controls. Sixteen (20%) of the patients were osteopenic in at least one site measured locations. The serum levels of 25-OH-VD3 were markedly reduced in the newly diagnosed SLE patients than those of the normal controls [(46.1+12.3) nmol/L vs. (25.4+11.2) nmol/L, P<0.001)]. The serum levels of 25-OH-VD3 in the SLE patients with nephritis were much lower than those without nephritis (P=0.04). A significant negative correlation was demonstrated between the serum concentration of 25-OH-VD3 and the disease activity scores as measured by SLE disease activity index (SLEDAI) (r=-0.3,P=0.001). The serum TRAP5b concentration was positively correlated with SLEDAI (r=0.435,P=0.003). Age (P=0.058) and SLEDAI (P=0.085) were probably associated with decreased BMD in Logistic regression analysis.@*CONCLUSION@#The study showed reduced BMD in untreated SLE patients. The role of chronic inflammation was of probable importance in bone metabolism.

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus / Vasculite digital inicial em uma grande coorte multicêntrica de pacientes com lúpus eritematoso sistêmico de início na infância

Abstract Objectives: To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Methods: Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. Results: DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p = 0.008), discoid rash (16% vs. 4%, p = 0.017), photosensitivity (76% vs. 45%, p = 0.002) and other cutaneous vasculitides (80% vs. 19%, p < 0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p = 0.003), fever (32% vs. 56%, p = 0.020) and hepatomegaly (4% vs. 23%, p = 0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p > 0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p = 0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p = 0.014) was significantly lower in the DV group. Conclusion: Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients.

Resumo Objetivos: Avaliar a vasculite digital (VD) clínica como uma manifestação inicial do lúpus eritematoso sistêmico de início na infância (LESi) em uma grande população. Métodos: Estudo transversal multicêntrico que incluiu 852 pacientes com LESi (critérios do ACR), acompanhados em dez centros de reumatologia pediátrica do Estado de São Paulo. Resultados: Observou-se VD em 25/852 (3%) pacientes com LESi. Diagnosticaram-se hemorragia periungueal em 12 (48%), infarto periungueal em sete (28%), úlcera de ponta de dígito em quatro (16%), nódulos dolorosos em um (4%) e gangrena em um (4%). Um desfecho ruim, com reabsorção digital, ocorreu em cinco (20%) pacientes. A comparação entre pacientes com e sem VD revelou maior frequência de erupção malar (80% vs. 53%, p = 0,008), erupção discoide (16% vs. 4%, p = 0,017), fotossensibilidade (76% vs. 45% p = 0,002) e outras vasculites cutâneas (80% vs. 19%, p < 0,0001), enquanto a frequência de características constitucionais totais (32% vs. 61%, p = 0,003), febre (32% vs. 56% p = 0,020) e hepatomegalia (4% vs. 23%, p = 0,026) foram menores nesses pacientes. A frequência do gênero feminino, o envolvimento grave de múltiplos órgãos, perfil de autoanticorpos e baixo complemento foram semelhantes nos dois grupos (p > 0,05). A mediana no Sledai-2 K, exclusive o descritor de VD, foi significativamente menor nos pacientes com VD em comparação com aqueles sem essa manifestação [10 (0 a 28) vs. 14 (0 a 58), p = 0,004]. Não foram observadas vasculite visceral nem morte nessa coorte de pacientes com LESi. A frequência de uso de ciclofosfamida (0% vs. 18%, p = 0,014) foi significativamente menor no grupo VD. Conclusão: Este grande estudo multicêntrico identificou a VD clínica como uma rara manifestação inicial do LESi ativo, associada a doença multissistêmica leve, apesar da ocorrência de reabsorção digital em alguns desses pacientes.

Poor muscle strength and function in physically inactive childhood-onset systemic lupus erythematosus despite very mild disease / Redução na força muscular e capacidade funcional em pacientes fisicamente inativos com lúpus eritematoso sistêmico de início juvenil, apesar de doença muito leve

ABSTRACT Objective: To compare muscle strength (i.e. lower- and upper-body strength) and function between physically inactive childhood-onset systemic lupus erythematosus patients (C-SLE) and healthy controls (CTRL). Methods: This was a cross-sectional study and the sample consisted of 19 C-SLE (age between 9 and 18 years) and 15 CTRL matched by age, sex, body mass index (BMI), and physical activity levels (assessed by accelerometry). Lower- and upper-body strength was assessed by the one-repetition-maximum (1-RM) test. Isometric strength was assessed through a handgrip dynamometer. Muscle function was evaluated by the timed-stands test (TST) and the timed-up-and-go test (TUG). Results: When compared with CTRL, C-SLE showed lower leg-press and bench-press 1-RM (p = 0.026 and p = 0.008, respectively), and a tendency toward lower handgrip strength (p = 0.052). C-SLE showed lower TST scores (p = 0.036) and a tendency toward higher TUG scores (p = 0.070) when compared with CTRL. Conclusion: Physically inactive C-SLE patients with very mild disease showed reduced muscle strength and functionality when compared with healthy controls matched by physical activity levels. These findings suggest C-SLE patients may greatly suffer from a physically inactive lifestyle than healthy controls do. Moreover, some sub-clinical “residual” effect of the disease or its pharmacological treatment seems to affect C-SLE patients even with a well-controlled disease.

RESUMO Objetivo: Comparar a força muscular (ou seja, a força muscular dos membros superiores e inferiores) e a capacidade funcional de pacientes fisicamente inativos com lúpus eritematoso sistêmico de início juvenil (LESJ) com controles saudáveis (CTRL). Métodos: Estudo transversal cuja amostra foi composta por 19 pacientes com LESJ (entre 9 e 18 anos) e 15 CTRL pareados por idade, sexo, índice de massa corporal (IMC) e nível de atividade física (avaliada através do uso de acelerômetros). A força dos membros superiores e inferiores foi avaliada pelo teste de uma repetição máxima (1-RM). A força isométrica foi avaliada através do uso de um dinamômetro. A capacidade funcional foi avaliada pelo Timed-stands test (TST) e Timed-up-and-go test (TUG). Resultados: Quando comparados com os CTRL, os pacientes com LESJ apresentaram menor força em 1-RM no Leg press e supino (p = 0,026 e p = 0,008, respectivamente) e uma tendência a menor força de preensão manual (p = 0,052). Os pacientes com LESJ apresentaram menores escores no TST (p = 0,036) e uma tendência a maior pontuação no TUG (p = 0,070), quando comparados com o grupo CTRL. Conclusão Pacientes com LESJ, fisicamente inativos, com doença muito leve mostraram redução na força muscular e capacidade funcional quando comparados com controles saudáveis pareados por níveis de atividade física. Esses achados sugerem que pacientes com LESJ podem apresentar mais efeitos deletérios por manter um estilo de vida fisicamente inativo do que controles saudáveis. Além disso, alguns efeitos “residuais” subclínicos da doença ou do tratamento farmacológico parecem afetar pacientes com LESJ, mesmo com uma doença bem controlada.

Influence of medical care in the quality of life (WHOQOL-100) of women living with systemic lupus erythematosus / Influência da atenção médica na qualidade de vida (WHOQOL-100) de mulheres com lúpus eritematoso sistêmico

ABSTRACT Lupus requires careful treatment by medical specialists. This study aimed to evaluate the quality of life of patients living with Systemic Lupus Erythematosus (SLE). The method approached women with a confirmed diagnosis of SLE under medical supervision in a University hospital outpatient clinic or in a private clinic. We used an instrument containing relevant information of the patient and also the Portuguese version of the World Health Organization Quality of Life Group (WHOQOL-100) questionnaire. The study population consisted of 39 women, married in their majority (56.4%); prevalently aged 37–60 years old; prevalence of diagnosis time over five years (66.7%); and in use of less than 5 medications (69.2%). 92.3% had the disease inactive with higher means in mobility (p = 0.0463) and quality of life (p = 0.0199) facets; on the other hand, the physical safety and security facet (p = 0.0093) showed higher mean for people with active disease. Health and social care analysis showed availability and quality (p = 0.0434), even when with other associated diseases (33.3%); and the highest means were Dependence on medicinal substances and medical aids (p = 0.0143). The negative results for associated diseases were higher in sexual activity (p = 0.0431) and transportation (p = 0.0319) facets. In conclusion: if women living with SLE receive continuous medical attention, they will enjoy good quality of life, while minimizing the complications inherent in this condition.

RESUMO O lúpus exige tratamento cuidadoso por médicos especialistas. Este estudo teve como objetivo avaliar a qualidade de vida de pacientes com lúpus eritematoso sistêmico (LES). O método abordou mulheres com diagnóstico confirmado de LES sob acompanhamento médico em ambulatório de hospital escola ou particular. Usou-se instrumento que continha informações relevantes do paciente e a versão em português do instrumento de pesquisa World Health Organization Quality of Life Group (WHOQOL-100). A população estudada perfez 39 mulheres, na sua maioria casadas (56,4%); com idade prevalente de 37 a 60 anos; tempo de diagnóstico prevalente maior de cinco anos (66,7%); uso de menos de cinco medicamentos (69,2%). Obteve-se que 92,3% estavam com a doença controlada com médias maiores nas facetas mobilidade (p = 0,0463) e qualidade de vida (p = 0,0199). Já a faceta segurança física e proteção (p = 0,0093) apresentou média maior para pessoas com a doença em estado ativado. As análises de cuidados de saúde e sociais apresentaram disponibilidade e qualidade (p = 0,0434) mesmo com outras patologias associadas (33,3%) e as maiores médias foram dependência de medicação ou de tratamentos (p = 0,0143). Os resultados negativos para doença associada foram maiores nas facetas atividade sexual (p = 0,0431) e transporte (p = 0,0319). Conclui-se que se a mulher com LES receber atenção médica de forma continua apresentará qualidade de vida que minimizará as complicações inerentes a essa patologia.

Linfócitos Th17 e linfócitos T CD4+ multifuncionais em pacientes com lúpus eritematoso sistêmico / Th17 cells and CD4+ multifunctional T cells in patients with systemic lupus erythematosus

Resumo Introdução/Objetivo: Evidências recentes sugerem que anormalidades que envolvem os linfócitos Th17 estão associadas à fisiopatologia do lúpus eritematoso sistêmico (LES). Além disso, os linfócitos T multifuncionais (LTM), ou seja, aqueles que produzem múltiplas citocinas simultaneamente, estão presentes no meio inflamatório e podem estar implicados no processo autoimune observado no LES. No presente estudo, objetiva-se caracterizar o estado funcional dos linfócitos T CD4+ no LES e determinar simultaneamente a concentração de IL-2, IFN-γ e IL-17 em culturas de linfócitos sob estímulos exógenos e autoantigênicos. Pacientes e métodos: Dezoito pacientes com doença ativa, 18 com doença inativa e 14 controles saudáveis foram submetidos à análise do estado funcional dos linfócitos T CD4+. Resultados: Encontrou-se que os pacientes com LES apresentaram uma diminuição na quantidade total de células CD4+, um aumento na quantidade de linfócitos T ativados e um aumento na frequência de linfócitos Th17 em comparação com controles saudáveis (HC). As células LTM tinha frequência aumentada em pacientes com LES e houve um aumento na frequência de LTM trifuncionais em pacientes com LES ativo em comparação com aqueles com LES inativo. Curiosamente, as células MTF produziram quantidades maiores de IFN-γ do que os linfócitos T monofuncionais em pacientes e controles. Conclusão: Analisados em conjunto, esses dados indicam a participação dos linfócitos Th17 recentemente ativados e células MTF na fisiopatologia do LES.

Abstract Introduction/Objective: Recent evidence suggests that abnormalities involving Th17 lymphocytes are associated with the pathophysiology of systemic lupus erythematosus (SLE). In addition, multifunctional T cells (MFT), i. e., those producing multiple cytokines simultaneously, are present in the inflammatory milieu and may be implicated in the autoimmune process observed in SLE. In the present study, we aimed to characterize the functional status of CD4+ T cells in SLE by simultaneously determining the concentration of IL-2, IFN-γ and IL-17 in lymphocyte cultures under exogenous and self-antigenic stimuli. Patients and methods: Eighteen patients with active disease, 18 with inactive disease, and 14 healthy controls had functional status of CD4+ T cells analyzed. Results: We found that SLE patients presented a decreased number of total CD4+ cells, an increased number of activated T cells, and an increased frequency of Th17 cells compared to healthy controls (HC). MFT cells had increased frequency in SLE patients and there was an increased frequency of tri-functional MFT in patients with active SLE compared with those with inactive SLE. Interestingly, MTF cells produced larger amounts of IFNγ than mono-functional T cells in patients and controls. Conclusion: Taken together these data indicate the participation of recently activated Th17 cells and MTF cells in the SLE pathophysiology.

Associação de imunodeficiência primária com lúpus eritematoso sistêmico: revisão da literatura e as lições aprendidas pela Divisão de Reumatologia de um hospital universitário terciário em São Paulo / Primary immunodeficiency association with systemic lupus erythematosus: review of literature and lessons learned by the Rheumatology Division of a tertiary university hospital at São Paulo, Brazil

Resumo As imunodeficiências primárias (IDP) representam um grupo heterogêneo de doenças resultantes de defeitos hereditários no desenvolvimento, na maturação e na função normal de células do sistema imunológico; assim, tornam os indivíduos suscetíveis a infecções recorrentes, alergia, autoimunidade e doenças malignas. Neste estudo retrospectivo descrevem-se doenças autoimunes (DAI), em especial o lúpus eritematoso sistêmico (LES), que surgiram associadas ao curso das IDP. Classicamente, a literatura descreve três grupos de IDP associadas ao LES: (1) deficiência de componentes da via do complemento, (2) defeitos na síntese de imunoglobulinas e (3) doença granulomatosa crônica (DGC). Na atualidade, outras IDP têm sido descritas como manifestações clínicas do LES, como a síndrome de Wiskott-Aldrich (WAS), a poliendocrinopatia autoimune-candidíase-distrofia ectodérmica (APECED), a síndrome linfoproliferativa autoimune (ALPS) e a linfocitopenia idiopática CD4+. Também são apresentados achados de uma coorte de adultos do ambulatório da Divisão de Reumatologia da Universidade Federal de São Paulo. As manifestações de IDP encontradas pelo nosso grupo de estudo foram consideradas leves em termos de gravidade de infecções e mortalidade no início da vida. Assim, é possível que alguns estados de imunodeficiência sejam compatíveis com a sobrevivência em relação à suscetibilidade infecciosa; no entanto, esses estados podem representar um fator de predisposição forte para o desenvolvimento de doenças imunológicas, como observado no LES.

Abstract Primary immunodeficiency disorders (PID) represent a heterogeneous group of diseases resulting from inherited defects in the development, maturation and normal function of immune cells; thus, turning individuals susceptible to recurrent infections, allergy, autoimmunity, and malignancies. In this retrospective study, autoimmune diseases (AIDs), in special systemic lupus erythematosus (SLE) which arose associated to the course of PID, are described. Classically, the literature describes three groups of PID associated with SLE: (1) deficiency of Complement pathway components, (2) defects in immunoglobulin synthesis, and (3) chronic granulomatous disease (CGD). Currently, other PID have been described with clinical manifestation of SLE, such as Wiskott–Aldrich syndrome (WAS), autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), autoimmune lymphoproliferative syndrome (ALPS) and idiopathic CD4+ lymphocytopenia. Also we present findings from an adult cohort from the outpatient clinic of the Rheumatology Division of Universidade Federal de São Paulo. The PID manifestations found by our study group were considered mild in terms of severity of infections and mortality in early life. Thus, it is possible that some immunodeficiency states are compatible with survival regarding infectious susceptibility; however these states might represent a strong predisposing factor for the development of immune disorders like those observed in SLE.

Terapia de reemplazo hormonal en LES: caso clínico / Hormone replacement therapy in SLE: clinical case

El uso de estrógeno en pacientes con Lupus Eritematoso Sistémico (LES) sigue siendo un tema en discusión, debido a los múltiples efectos que esta hormona puede tener en el sistema inmune; entre los cuales incluso se ha postulado un rol promotor de esta enfermedad. Se presenta el caso de una paciente de 28 años con diagnóstico de LES, asociado a falla ovárica y osteoporosis en la cual se debe utilizar terapia de reemplazo hormonal (TRH) y se discuten sus posibles consecuencias.

Estrogen use in patients with Systemic Lupus Erythematosus (SLE) is still a matter under discussion, due to the multiple effects that this hormone can have on the immune system; it has been postulated a promoter role of this disease. The case of a patient of 28 years with a diagnosis of SLE associated with ovarian failure and osteoporosis in which to use hormone replacement therapy (HRT) and its possible consequences are discussed is presented.