Papel del IFN-λ en la patogénesis del Lupus eritematoso sistémico: mecanismos Biomoleculares

Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune que causa inflamación sistémica y alteraciones en la tolerancia inmunológica. La activación de los genes inducibles por interferón (IFN), contribuye en más del 50% de su patogenia. Objetivo: relacionar el papel del IFN-λ en la patogenia del LES. Materiales y Métodos: Búsqueda sistémica en base de datos; a través de las palabras claves del MeSH and DeCS. Fue incluido adicionalmente la palabra "Interferón Lambda". Resultados: Se encontró que la producción aberrante de interferón tipo I contribuye a la desregulación de IFN-λ, producido principalmente por células dendríticas plasmocitoides. Este proceso conduce a la estimulación inmunológica por autoanticuerpos y a un aumento de IFNλR-1 en células B, potenciando la generación de anticuerpos. IFN-λ3 se asocia particularmente con nefritis lúpica, y el IFN-λ en general aumenta la expresión de MHC-I, intensificando la respuesta de células T CD8+ y posiblemente afectando la tolerancia central y la regulación en el timo. Conclusión: Se destaca que el IFN-λ favorece la activación inmune, formación de inmunocomplejos, inflamación crónica y producción de autoanticuerpos, vinculándose niveles altos de IFN-λ3 con mayor actividad de la enfermedad.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease that causes systemic inflammation and alterations in immunological tolerance. The activation of interferon (IFN)-inducible genes contributes to more than 50% of its pathogenesis. Objective: to review the role of IFN-λ in the pathogenesis of SLE. Materials and Methods: Systemic search in database; through the MeSH and DeCS keywords. The word "Lambda Interferon" was additionally included. Results: Aberrant production of type I interferon was found to contribute to the deregulation of IFN-λ, produced mainly by plasmacytoid dendritic cells. This process leads to immunological stimulation by autoantibodies and an increase in IFNλR-1 in B cells, enhancing the generation of antibodies. IFN-λ3 is particularly associated with lupus nephritis, and IFN-λ generally increases MHC-I expression, enhancing the CD8+ T cell response and possibly affecting central tolerance and regulation in the thymus. Conclusion: It is highlighted that IFN-λ favors immune activation, formation of immune complexes, chronic inflammation and production of autoantibodies, linking high levels of IFN-λ3 with greater disease activity.

Síndrome antifosfolipídico trombótico en una mujer con enfermedad mixta del tejido conectivo. Reporte de caso / Thrombotic antiphospholipid syndrome in a woman with mixed connective tissue disease. Case report

Introducción: El síndrome de anticuerpos antifosfolípidos es una enfermedad au-toinmune sistémica poco frecuente, produce hipercoagulabilidad con riesgo de trombosis. Para el diagnóstico se utilizan los criterios ACR/EULAR APS del 2023. El tratamiento es anticoagulantes y antiagregantes plaquetarios. La enfermedad mixta del tejido conectivo es enfermedad autoinmunitaria sistémica con la asociación de manifestaciones clínicas de otras entidades autoinmunes. Objetivo:Describir la presentación de dos enfermedades sistémicas autoinmunes poco frecuentes en conjunto, con el propósito de contribuir con un enfoque prác-tico para el diagnóstico y manejo. Presentación del caso: Se describe una paciente de 37 años que presentó un episodio de tromboembolia pulmonar secundario a síndrome de anticuerpos anti-fosfolípidos y en los 6 meses previos tuvo síntomas compatibles con enfermedad mixta del tejido conectivo. Discusión: La presencia de dos entidades autoinmunes, síndrome de anticuerpos antifosfolípidos y enfermedad mixta del tejido conectivo presentadas en conjunto y cuyo debut de complicaciones fue una tromboembolia pulmonar, encontrándo-se presencia de múltiples autoanticuerpos positivos entre estas anticuerpos an-tifosfolipídicos y anti-U1 snRNP, es un reto diagnóstico al diferenciar entre otras enfermedades del tejido conectivo como lupus eritematoso sistémico, esclerosis sistémica cutánea, enfermedad mixta del tejido conectivo y artritis reumatoide. El tratamiento se basó en las características del paciente y su condición clínica al momento del diagnóstico. Conclusiones: El síndrome de anticuerpos antifosfolipídicos conlleva la presencia de un episodio trombótico, por otro lado, su asociación con una enfermedad mixta del tejido conectivo es poco frecuente y puede aumentar su morbimortalidad.

Introduction: Antiphospholipid antibody syndrome is a rare systemic autoimmu-ne disease that produces Antiphospholipid antibody syndrome is a rare systemic autoimmune disease that causes hypercoagulability with risk of thrombosis. For diagnosis, the ACR/EULAR APS 2023 criteria are used. Treatment is anticoagulants and antiplatelet agents.Mixed connective tissue disease is a systemic autoimmune disease with the asso-ciation of clinical manifestations of other autoimmune entities.Objective:To describe the presentation of two rare autoimmune systemic diseases toge-ther, with the purpose of contributing a practical approach to diagnosis and management.Case presentation: 37-year-old patient with an episode of pulmonary thromboem-bolism secondary to antiphospholipid antibody syndrome and in the previous 6 months he had symptoms compatible with mixed connective tissue disease.Discussion:The presence of two autoimmune entities, antiphospholipid antibody syndrome and mixed connective tissue disease presented together and whose de-but of complications was a pulmonary thromboembolism, finding the presence of multiple positive autoantibodies between these antiphospholipid antibodies and an-ti-U1 snRNP, is a diagnostic challenge in differentiating between other connective tissue diseases such as systemic lupus erythematosus, cutaneous systemic sclero-sis, mixed connective tissue disease and rheumatoid arthritis. Treatment was based on the patient's characteristics and clinical condition at the time of diagnosis.Conclusions: Antiphospholipid antibody syndrome entails the presence of a thrombotic episode; on the other hand, its association with a mixed connective tissue disease is rare and may increase its morbidity and mortality.

Value of precision nutrition in the inflammatory control of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies directed against endogenous antigens causing various clinical manifestations, chronic inflammation and tissue damage. Although the pathophysiology of SLE remains unknown, it is recognized that genetic, epigenetic, environmental and neuroendocrine factors are involved in the development of the disease and its complications. A notable proportion of patients with SLE also present obesity, and this dysmetabolic profile can cause renal, musculoskeletal and/or respiratory deterioration, fatigue, various pathophysiological alterations and functional deterioration. In this context, precision nutrition emerges as a promising tool in the inflammatory control of SLE, especially in patients with associated obesity. Various studies demonstrate the beneficial influence of balanced dietary patterns in macronutrients with foods rich in fiber, vitamins, minerals, antioxidants and polyphenols on the inflammatory control of SLE and the most diverse pathologies, highlighting the Mediterranean diet and plant-based diets. Finally, the intestinal microbiota may play a relevant role in this clinical scenario, since dysbiosis is associated with inflammatory processes and immune deregulation. It is believed that precision nutrition can modulate inflammatory profiles and immune dysfunctions to ensure better quality of life and metabolic well-being of SLE patients with the support of precision omics technologies.

El lupus eritematoso sistémico (LES) es una enfermedad autoinmune caracterizada por la producción de autoanticuerpos dirigidos contra antígenos endógenos causando diversas manifestaciones clínicas, inflamación crónica y daño tisular. Aunque la fisiopatología del LES sigue siendo desconocida, se reconoce que factores genéticos, epigenéticos, ambientales y neuroendocrinos están implicados en el desarrollo de la enfermedad y sus complicaciones. Una proporción notable de pacientes con LES presenta también obesidad, y este perfil dismetabólico puede producir deterioro renal, musculoesquelético y/o respiratorio, fatiga, diversas alteraciones fisiopatológicas y deterioro funcional. En este contexto, la nutrición de precisión emerge como una herramienta prometedora en el control inflamatorio del LES, especialmente en pacientes con obesidad asociada. Diversos estudios demuestran la influencia beneficiosa de patrones dietéticos equilibrados en macronutrientes con alimentos ricos en fibra, vitaminas, minerales, antioxidantes y polifenoles en el control inflamatorio del LES y de las más diversas patologías, destacando la dieta Mediterránea y las dietas basadas en plantas/vegetales. Por último, la microbiota intestinal puede tener un papel relevante en este escenario clínico, ya que la disbiosis se asocia con procesos inflamatorios y desregulación inmune. Se cree que con la nutrición de precisión se pueden modular los perfiles inflamatorios y las disfunciones inmunitarias para garantizar una mejor calidad de vida y el bienestar metabólico de los pacientes con LES con el apoyo de las tecnologías de precisión ómicas.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block / Prevalencia de lupus neonatal en un pequeño grupo de madres portadoras de anticuerpos y frecuencia de bloqueo auriculoventricular completo

Abstract Background: Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. Objective: To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. Methods: From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. Results: Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. Conclusions: CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

Resumen Antecedentes: El lupus neonatal (LN) es extremadamente raro y es ocasionado por el paso transplacentario de auto-anticuerpos maternos IgG contra las proteínas Ro, La y/o RNP a la circulación fetal que puede ocasionar bloqueo aurículo-ventricular completo congénito (BAVCC) permanente, lesiones dérmicas y afectación hepática. Objetivo: Conocer la prevalencia de LN en paciente con BAVCC y la evolución clínica en un seguimiento a largo plazo. Métodos: De enero de 1992 a diciembre 2017 se incluyeron paciente con BAVCC. La presencia de anticuerpos antinucleares anti-SSA/Ro y anti-SSB/La en suero materno confirmó LN. Resultados: Ocho pacientes fueron incluidos con seguimiento de 10 ± 6 años, el 62.5 % con LN; dos fueron del sexo masculino. Uno diagnosticado in útero, dos al nacimiento, en ellos se implantó marcapaso; uno a los 12 años de edad y otro a los 15. Los otros dos casos fueron diagnosticados a los 18 y 26 años, se implantó marcapaso definitivo en ellos 8 y 5 años después respectivamente. En un caso no se implantó marcapaso definitivo; un recién nacido con solo un año de seguimiento. Al dar a luz, el 60 % de las madres estaban libres de enfermedad reumática y en conjunto todas tuvieron 19 hijos, ninguno de ellos presentó manifestaciones de LN. Conclusiones: El BAVCC es raro y frecuentemente está asociado a una enfermedad autoinmune materna, prácticamente todos requerirán de marcapaso definitivo en alguna época de su vida.

Seguridad de la vacunación COVID-19 en una muestra de pacientes brasileños con lupus eritematoso sistémico / Safety of COVID-19 vaccination in a sample of Brazilian patients with systemic lupus erythematosus patients

Objetivos: estudiar los efectos secundarios y el riesgo de exacerbación de la en-fermedad después de la vacunación COVID-19 en una muestra de pacientes con lupus eritematoso sistémico (LES). Materiales y métodos: estudio retrospectivo que investigó 101 pacientes con LES. Se determinó la actividad de la enfermedad mediante el Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) antes y después de dos dosis de la vacuna contra el SARS-COv-2. Se registraron los efectos secundarios después de la vacunación. Resultados: los pacientes que recibieron dos dosis de la misma vacuna fue-ron el 10,3% para CoronaVAc, el 42,2% para Pfizer y el 47,3% para AstraZeneca. Se detectaron efectos secundarios en el 76,2% y la mayoría fue leve/moderado. Los más frecuentes fueron: dolor local (62,3%), cefalea (36,6%) y fatiga (34,6%). El cambio en la mediana del SLEDAI antes de la primera dosis y después de la segunda no fue estadísticamente significativo (p=0,68). Solo el 4,1% de los individuos aumentó el SLEDAI ≥ de 3 puntos. Conclusiones: la vacunación contra la COVID-19 fue bien tolerada y segura en pacientes con LES.

Objectives: to study the side effects and the risk of disease flare after COVID-19 vaccination in Brazilian patients with Systemic Lupus erythematosus (SLE). Materials and methods: this retrospective study investigated a sample of 101 SLE patients for disease activity through the SLE disease activity index (SLEDAI) prior to and after two vaccine doses against SARS-COv-2. Side effects after vaccination were recorded. Results: in this sample, patients receiving two doses of the same vaccine were 10.3% for CoronaVAc; 42.2% for Pfizer, and 47.3% for AstraZeneca. Side effects were detected in 76.2% of them, and most of them were mild and moderate; the most common were local pain (62.3%), headache (36.6%), and fatigue (34.6%). The SLEDAI prior to the first dose and after the second dose did not change significantly (p=0.68). Only 4.1% of individuals had increased in SLEDAI ≥than 3 points. Conclusions: vaccination against COVID-19 was well tolerated and safe in SLE patients

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

Abstract Background: Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE). Objective: To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays. Methods: Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems. Results: Skin samples from CLE/SLE +patients presented higher expression of IL-1β (ARC-82: p = 0.024; SLICC-12: p = 0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p = 0.0097; SLICC-12: p = 0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p = 0.0003; SLICC-12: p = 0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p = 0.0257; SLICC-12: p = 0.0285) and CD8+ cells (ARC-82: p = 0.0075; SLICC-12: p = 0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p = 0.0024; SLICC-12: p = 0.0116). Study limitations: Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years. Conclusions: In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

Infecciones más frecuentes en pacientes con Lupus Eritematoso Sistémico internados en el Servicio de Clínica Médica del Hospital Nacional / Most frequent infections in patients with Systemic Lupus Erythematosus admitted to the Medical Clinic Service of the Hospital Nacional

Introducción: el lupus eritematoso sistémico (LES) se conoce como una enfermedad autoinmune multisistémica, cuya causa es desconocida, se caracteriza por la presencia de complejos inmunes y autoanticuerpos. En series internacionales se describe una presentación de procesos infecciosos en estos pacientes hasta en un 75 % de los casos, las infecciones ocurren tanto al inicio de la enfermedad como en etapas tardías, y son causa directa de muerte en 30 % a 60 % de los casos y motivo de hospitalización hasta de 30 %. Objetivos: determinar los procesos infecciosos más frecuentes en pacientes con lupus eritematoso sistémico internados en el Servicio de Clínica Médica del Hospital Nacional en el periodo 2022-2023. Metodología: diseño observacional, descriptivo de corte transversal de pacientes con diagnóstico de lupus eritematoso sistémico según criterios de European League Against Rheumatism (EULAR)-2019 que se encuentran internados en el servicio de Clínica Médica del Hospital Nacional (Itaugua-Paraguay) en el periodo de 2022-2023. Resultados: la edad media de los pacientes fue de 34 años, con predominio del sexo femenino en el 88.18 %. Las infecciones del aparato respiratorio fue la más frecuentemente diagnosticada en 50 (45.45 %) pacientes, seguido por la infección de vías urinarias 47 (42.38 %) pacientes, el condicionante de riesgo predominante fue el uso de corticoides en un total 105 (96.40 %) pacientes, se estableció en un total de 97 (88.18 %) pacientes con antibioticoterapia, dentro del aspecto demográfico de la zona urbana 56 (50.90 %) pacientes y rural 54(49.1 %). Conclusión: la infección del aparato respiratorio fue la infección más frecuente, el condicionante de riesgo predominante es el uso de corticoides y recibieron antibioticoterapia la cual en monoterapia fue la más utilizada

Introduction: systemic lupus erythematosus (SLE) is known as a multisystem autoimmune disease, whose cause is unknown, and is characterized by the presence of immune complexes and autoantibodies. In international series, presentation of infectious processes is described in these patients in up to 75 % of cases. Infections occur both at the beginning of the disease and in late stages, and are a direct cause of death in 30 % to 60 % of patients. Cases and reason for hospitalization up to 30 %. Objectives: determine the most frequent infectious processes in patients with systemic lupus erythematosus admitted to the Medical Clinic Service of the Hospital Nacional in the period 2022-2023. Methodology: observational, descriptive cross-sectional design of patients with a diagnosis of systemic lupus erythematosus according to criteria of European League Against Rheumatism (EULAR)-2019 who are admitted to the Medical Clinic service of the Hospital Nacional (Itauguá-Paraguay) in the period of 2022-2023. Results: the average age of the patients was 34 years, with a predominance of the female sex in 88.18 %. Respiratory system infections were the most frequently diagnosed in 50 (45.45 %) patients, followed by urinary tract infection in 47 (42.38 %) patients. The predominant risk factor was the use of corticosteroids in a total of 105 (96.40 %) patients, it was established in a total of 97 (88.18 %) patients with antibiotic therapy, within the demographic aspect of the urban area 56 (50.90 %) patients and rural 54 (49.1 %). Conclusion: respiratory tract infection was the most frequent infection, the predominant risk factor is the use of corticosteroids and they received antibiotic therapy, which in monotherapy was the most used.

Seguridad de la vacunación COVID-19 en una muestra de pacientes brasileños con lupus eritematoso sistémico

Abstract Objectives: to study the side effects and the risk of disease flare after COVID-19 vaccination in Brazilian patients with Systemic Lupus erythematosus (SLE). Materials and methods: this retrospective study investigated a sample of 101 SLE patients for disease activity through the SLE disease activity index (SLEDAI) prior to and after two vaccine doses against SARS-COv-2. Side effects after vaccination were recorded. Results: in this sample, patients receiving two doses of the same vaccine were 10.3% for CoronaVAc; 42.2% for Pfizer, and 47.3% for Astra-Zeneca. Side effects were detected in 76.2% of them, and most of them were mild and moderate; the most common were local pain (62.3%), headache (36.6%), and fatigue (34.6%). The SLEDAI prior to the first dose and after the second dose did not change significantly (p=0.68). Only 4.1% of individuals had increased in SLEDAI ≥than 3 points. Conclusions: vaccination against COVID-19 was well tolerated and safe in SLE patients.

Resumen Objetivos: estudiar los efectos secundarios y el riesgo de exacerbación de la enfermedad después de la vacunación COVID-19 en una muestra de pacientes con lupus eritematoso sistémico (LES). Materiales y métodos: estudio retrospectivo que investigó 101 pacientes con LES. Se determinó la actividad de la enfermedad mediante el Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) antes y después de dos dosis de la vacuna contra el SARS-COv-2. Se registraron los efectos secundarios después de la vacunación. Resultados: los pacientes que recibieron dos dosis de la misma vacuna fueron el 10,3% para CoronaVAc, el 42,2% para Pfizer y el 47,3% para AstraZeneca. Se detectaron efectos secundarios en el 76,2% y la mayoría fue leve/moderado. Los más frecuentes fueron: dolor local (62,3%), cefalea (36,6%) y fatiga (34,6%). El cambio en la mediana del SLEDAI antes de la primera dosis y después de la segunda no fue estadísticamente significativo (p=0,68). Solo el 4,1% de los individuos aumentó el SLEDAI ≥ de 3 puntos. Conclusiones: la vacunación contra la COVID-19 fue bien tolerada y segura en pacientes con LES.

Generation and characterization of humanized monoclonal antibody against human IFNAR1 / 中国药科大学学报

@#Abstract: Type I interferons play an important role in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE). Monoclonal antibody shows therapeutic potential by blocking the signaling pathway. This study used recombinant human subunit 1 of the type I interferon receptor (IFNAR1) protein to immunize New Zealand white rabbits, and applied B cell cloning technology to screen and obtain rabbit parental antibodies. After humanization modification, QX006N was obtained. In vitro biological studies showed that QX006N could specifically bind to human IFNAR1 with an affinity of 108 pmol/L, and neutralize the type I interferon signaling pathway and this pathway mediated biological effects. This study provides a solid foundation for the development of antibody drugs targeting the type I interferon signaling pathway for the treatment of SLE.

Continuous Unilateral Cephalalgia Due to Systemic Lupus Erythematosus: A Case Report / Cefaleia unilateral contínua por lúpus eritematoso sistêmico: relato de caso

BACKGROUND: Hemicrania continua is a rare form of cephalalgia featuring a chronic and persistent headache in only one side of the head. OBJECTIVES: In this report, we present a case of a patient with hemicrania continua and systemic lupus erythematosus (SLE). METHODS: We collected patient data through the electronic medical record. Afterward, we reviewed the literature regarding hemicrania continua and its pathophysiology and correlation with neurovascular alterations, inflammation, and SLE. RESULTS: A 42-year-old woman visited the emergency department due to worsening constant unilateral cephalalgia that had been present for the past 6 months. The patient reported a highly intense (10/10) headache in the entire left hemicrania that radiated to the left shoulder. During physical examination, she presented with nystagmus, vertigo, and aggravated cephalalgia associated to body movement and, despite having no optic nerve thickening. In addition, she had jaundice, tachycardia, and splenomegaly. Complimentary exams found deep anemia, depletion in complement system and anti-nuclear factors, suggesting a possible hemolytic anemia (AIHA) due to SLE. Treatment was initiated with hydrocortisone and prednisone, associated with amitriptyline, fluoxetine and diazepam, reaching full remission. CONCLUSION: These syndromes have aggravated each other, and possibly the explanation for the cephalalgia remission was the control of AIHA and SLE. It features a rare case in literature and thus warrants discussion.

INTRODUÇÃO: Hemicrania contínua é uma forma rara de cefaléia caracterizada por cefaleia crônica e persistente em apenas um lado da cabeça. OBJETIVOS: Neste relato apresentamos o caso de um paciente com hemicrania contínua e lúpus eritematoso sistêmico (LES). MÉTODOS: Coletamos dados dos pacientes por meio do prontuário eletrônico. Posteriormente, revisamos a literatura sobre a hemicrania contínua e sua fisiopatologia e correlação com alterações neurovasculares, inflamação e LES. RESULTADOS: Uma mulher de 42 anos recorreu ao serviço de urgência devido ao agravamento da cefaleia unilateral constante, presente nos últimos 6 meses. O paciente relatou cefaleia de alta intensidade (10/10) em toda a hemicrânia esquerda com irradiação para o ombro esquerdo. Ao exame físico apresentava nistagmo, vertigem e cefaléia agravada associada à movimentação corporal e, apesar de não apresentar espessamento do nervo óptico. Além disso, ela apresentava icterícia, taquicardia e esplenomegalia. Os exames complementares evidenciaram anemia profunda, depleção do sistema complemento e fatores antinucleares, sugerindo uma possível anemia hemolítica (AIHA) por LES. Iniciou-se tratamento com hidrocortisona e prednisona, associadas a amitriptilina, fluoxetina e diazepam, atingindo remissão completa. CONCLUSÃO: Essas síndromes agravaram-se mutuamente e possivelmente a explicação para a remissão da cefaléia foi o controle da AIHA e do LES. Apresenta um caso raro na literatura e, portanto, merece discussão.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

What is known about the effects of vitamin D in neuropsychiatric lupus?

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect several organs and systems. The central and/or peripheral nervous system can suffer from complications known as neuropsychiatric lupus (NPSLE). Studies have associated the manifestations of SLE or NPSLE with vitamin D deficiency. It has been shown that hypovitaminosis D can lead to cognition deficits and cerebral hypoperfusion in patients with NPSLE. In this review article, we will address the main features related to vitamin D supplementation or serum vitamin D levels with neuropsychiatric manifestations, either in patients or in animal models of NPSLE.

Characterization of the patterns of care, access, and direct cost of systemic lupus erythematosus in Brazil: findings from the Macunaíma study

Abstract Background A cost of illness (COI) study aims to evaluate the socioeconomic burden that an illness imposes on society as a whole. This study aimed to describe the resources used, patterns of care, direct cost, and loss of productivity due to systemic lupus erythematosus (SLE) in Brazil. Methods This 12-month, cross-sectional, COI study of patients with SLE (ACR 1997 Classification Criteria) collected data using patient interviews (questionnaires) and medical records, covering: SLE profile, resources used, morbidities, quality of life (12-Item Short Form Survey, SF-12), and loss of productivity. Patients were excluded if they were retired or on sick leave for another illness. Direct resources included health-related (consultations, tests, medications, hospitalization) or non-health-related (transportation, home adaptation, expenditure on caregivers) hospital resources. Costs were calculated using the unit value of each resource and the quantity consumed. A gamma regression model explored cost predictors for patients with SLE. Results Overall, 300 patients with SLE were included (92.3% female, mean [standard deviation (SD)] disease duration 11.8 [7.9] years), of which 100 patients (33.3%) were on SLE-related sick leave and 46 patients (15.3%) had stopped schooling. Mean (SD) travel time from home to a care facility was 4.4 (12.6) hours. Antimalarials were the most commonly used drugs (222 [74.0%]). A negative correlation was observed between SF-12 physical component and SLE Disease Activity Index (- 0.117, p = 0.042), Systemic Lupus International CollaboratingClinics/AmericanCollegeofRheumatology Damage Index (- 0.115, p = 0.046), medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific drugs/day (- 0.113, p = 0.051), and lost productivity (- 0.570, p < 0.001). For the mental component, a negative correlation was observed with medications/day for multiple co-morbidities (- 0.272, p < 0.001), SLE-specific medications/day (- 0.113, p = 0.051), and missed appointments (- 0.232, p < 0.001). Mean total SLE cost was US$3,123.53/patient/year (median [interquartile range (IQR)] US$1,618.51 [$678.66, $4,601.29]). Main expenditure was medication, with a median (IQR) cost of US$910.62 ($460, $4,033.51). Mycophenolate increased costs by 3.664 times (p < 0.001), and inflammatory monitoring (erythrocyte sedimentation rate or C-reactive protein) reduced expenditure by 0.381 times (p < 0.001). Conclusion These results allowed access to care patterns, the median cost for patients with SLE in Brazil, and the differences across regions driven by biological, social, and behavioral factors. The cost of SLE provides an updated setting to support the decision-making process across the country.

Pregnancy loss in women with systemic lupus erythematosus: Grounded Theory / Pérdida del embarazo en mujeres con lupus eritematoso sistémico: una Teoría Fundamentada en Datos / Perda gestacional por mulheres com Lúpus Eritematoso Sistêmico: uma Teoria Fundamentada nos Dados

ABSTRACT Objective: to learn the meanings attributed to pregnancy loss by women with Lupus. Method: qualitative research, based on Symbolic Interactionism and Grounded Theory. Data collection took place between January and August 2022 through in-depth interviews. Data analysis went through the stages of initial and focused coding. Results: seventeen women participated. The central phenomenon "The climb to motherhood: falls and overcoming" was constructed, consisting of three categories: "Falling to the ground during the climb: the experience of pregnancy loss"; "Getting up and following the path: new attempts to conceive"; and "Remembering the journey: meanings attributed to pregnancy losses". Final considerations: experiencing pregnancy is, analogously, like climbing a mountain, where obstacles need to be overcome to reach the summit. The experience of pregnancy loss is seen as complex, especially when there is fragility in healthcare and a lack of awareness regarding feelings of loss and grief.

RESUMEN Objetivo: comprender los significados atribuidos a la pérdida del embarazo por mujeres con Lupus. Método: investigación cualitativa, basada en el Interaccionismo Simbólico y la Teoría Fundamentada en Datos. La recolección de datos se realizó entre enero y agosto de 2022, mediante entrevistas en profundidad. El análisis de datos pasó por las etapas de codificación inicial y focalizada. Resultados: participaron 17 mujeres. Se construyó el fenómeno central "La subida a la maternidad: caídas y superación", conformado por tres categorías: "Caer al suelo durante la subida: la experiencia de la pérdida del embarazo"; "Levantarse y seguir el camino: nuevos intentos de concebir"; y "Recordando el viaje: significados atribuidos a las pérdidas de embarazos". Consideraciones finales: vivir el embarazo es, análogamente, como escalar una montaña, donde es necesario superar obstáculos para llegar a la cima. La experiencia de la pérdida del embarazo se considera compleja, especialmente cuando hay fragilidad en la atención de salud y falta de conciencia sobre los sentimientos de pérdida y duelo.

RESUMO Objetivo: apreender os significados atribuídos à perda gestacional por mulheres com lúpus. Método: pesquisa qualitativa, pautada no Interacionismo Simbólico e na Teoria Fundamentada nos Dados. A coleta de dados ocorreu entre janeiro e agosto de 2022, mediante entrevistas em profundidade. A análise de dados percorreu as etapas de codificação inicial e focalizada. Resultados: participaram 17 mulheres. Construiu-se o fenômeno central "A escalada da maternidade: quedas e superações", constituído por três categorias: "Caindo ao chão durante a subida: a vivência da perda gestacional"; "Levantando e seguindo o caminho: novas tentativas de gestar"; e "Rememorando o percurso: significados atribuídos às perdas gestacionais". Considerações finais: vivenciar a gestação é, analogicamente, como escalar uma montanha, onde obstáculos precisam ser vencidos até o alcance do cume. A vivência de perdas gestacionais é significada como complexa, em especial quando há fragilidade na assistência à saúde e falta de sensibilização diante dos sentimentos de perda e luto.

Research progress on the manifestations and prognosis of neonatal lupus erythematosus in various systems / 中国当代儿科杂志

Neonatal lupus erythematosus (NLE) is caused by the transmission of maternal anti-Ro/SSA antibodies, anti-La/SSB antibodies, and other autoantibodies to the fetus through the placenta. Usually, with the disappearance of autoantibodies in the children's body, abnormal changes in the mucocutaneous, blood system, and digestive system can spontaneously subside, but the damage to various systems caused by autoantibodies may persist for a long time. This article provides a comprehensive review of the manifestations and prognosis of NLE in various systems, including mucocutaneous, blood system, circulatory system, nervous system, digestive system, respiratory system, aiming to provide reference for clinical work.

Establishment and evaluation of nomogram for differential diagnosis of systemic lupus erythematosus based on laboratory indications / 上海交通大学学报（医学版）

Objective·To establish a nomogram for the differential diagnosis of early systemic lupus erythematosus(SLE)and other autoimmune diseases based on laboratory indications,and to evaluate its efficacy.Methods·A total of 535 SLE patients admitted to the First Hospital of Lanzhou University from January 2017 to December 2021 were selected as SLE group,and 535 patients with other autoimmune diseases during the same period were selected as control group.Basic information and laboratory test indicators of the SLE group and control group were collected and compared.The SLE group and control group were randomly assigned to the training set and the validation set at a ratio of 7∶3,respectively.LASSO regression method and multivariate Logistic regression were used to select the main risk factors of SLE.The nomogram for differential diagnosis of early SLE(SLE nomogram)was established according to the selected main risk factors.Bootstrap method was used to conduct internal repeated sampling for 1 000 times to calibrate the nomogram.The receiver operator characteristic curve(ROC curve)and decision curve analysis(DCA)were performed to evaluate the differential diagnosis ability and the value in clinical application of SLE nomogram,respectively.The"DynNom"package of R language was used to convert the nomogram into an electronic calculator,and its consistency with SLE nomogram was verified by data from 3 groups of patients.Results·LASSO regression and multivariate Logistic regression identified six major risk factors for SLE,including antinuclear antibody(ANA),anti-double-stranded DNA(anti-dsDNA)antibody,anti-ribonucleoprotein antibody/anti-Simth antibody(anti-nRNP/Sm),anti-ribosomal P protein(anti-P)antibody,anti-nucleosome antibody(ANuA)and urinary protein(PRO),which were used to construct the SLE nomogram.The calibration curve of the SLE nomogram had standard errors of 0.009 and 0.015 in the training set and validation set,respectively,and its area under the curve(AUC)was 0.889 and 0.869,respectively.The results of DCA showed that when the risk threshold of SLE nomogram was 0.15?0.95,the model achieved more net benefit.The prediction results of the electronic calculator showed that when ANA(titer 1∶100)was positive in SLE patient No.1,the prevalence was 0.166;when both ANA(titer 1∶100)and ANuA(titer 1∶100)were positive in patient No.2,the prevalence was 0.676;when all of PRO,ANA(titer 1∶100),ANuA(titer 1∶100)and anti-P antibody(titer 1∶100)were positive in patient No.3,the prevalence was 0.990,which was consistent with the differential diagnosis results of the SLE nomogram.Conclusion·The established SLE nomogram based on ANA,anti-dsDNA antibody,anti-nRNP/Sm,anti-P antibody,ANuA and PRO and its conversion into an electronic calculator can effectively distinguish early SLE from other autoimmune diseases,and have important clinical application value.

The Experience of AI Rudi in Staged Differentiation and Treatment of Systemic Lupus Erythematosus / 中医杂志

This article summarized the clinical experience of Professor AI Rudi in staged treatment according to pattern differentiation of systemic lupus erythematosus （SLE）. It is believed that SLE is characterized by kidney yin deficiency and heat toxin obstruction as the core disease mechanism. The staged treatment principle is to nourish yin and clear heat， invigorate blood and resolve toxins. In the early stage of heat toxins accumulation， the focus is on treating the branch and strengthen the kidneys as early as possible， recommending self-designed Liangxue Xiaofeng Powder （凉血消风散） with modifications. In the middle stage， there is yin deficiency with internal heat， which requires nourishing kidney yin and eliminating pathogenic factors. The prescription suggested is self-designed Shouwu Dihuang Decoction （首乌地黄汤）. In the late stage， there is yin impairment affecting yang， which requires a gradual consolidation of the foundation and harmonization of yin and yang， usually with Zhenwu Decoction （真武汤） and Zishen Tongguan Powder （滋肾通关散） with modifications. At the same time， the treatment emphasizes the integration of Chinese and Western medicine， and use of self-designed Ershen Dihuang Pill （二参地黄丸） after initial remission to consolidate the effect and prevent relapse. External treatment should also be given importance to， and Hongyou Ointment （红油膏） can be used to treat SLE skin lesions， reduce swelling， and relieve pain.

Association of anti-neutrophil cytoplasmic antibodies with the disease activity in patients with systemic lupus erythematosus / 实用医学杂志

Objective To investigate the clinical significance of ANCA in the disease activity of patients with SLE.Methods A total of 1 025 SLE patients were recruited and were divided into inactive and active groups according to SLEDAI score.Demographic characteristics,clinical symptoms,autoantibodies,routine laboratory tests and renal pathology were also recorded and compared between the two groups.Results All patients were divided into inactive group(n = 750)and active group(n = 250).The occurrence of renal,pulmonary,cutaneous,arthritis manifestations were significantly higher than those of the inactive group(all P<0.05).All patients were tested for ANCA,and the most common pattern being perinuclear or p-ANCA,the percentage of p-ANCA seroposi-tive increased greatly with the increased disease activity(P<0.05).The autoantibodies were further analyzed between the two groups,25 patients had reactivity to MPO,but no patient had reactivity to PR3.Also,there were significant differences in anti-dsDNA antibody,anti-nucleosome antibody between the two groups(P<0.05).In the active group,patients with p-ANCA seropositive exhibited higher serum beta-2-microglobulin(β2-MG),titers of anti-dsDNA antibody,SLEDAI scores,lower albumin,C3,and C4 levels(P<0.05).Meanwhile,p-ANCA was associated with IL-6,which increased significantly with the increase of SLEDAI score.In addition,patients with p-ANCA seropositive had more occurrence of lupus nephritis,but it had no association with the renal pathology.Conclusion The appearance of p-ANCA in SLE patients indicated more severe disease activity status.

Evaluation value of magnetic resonance diffusion tensor imaging for cerebrovascular small vessel disease in patients with systemic lupus erythematosus / 中国医师进修杂志

Objective:To explore the value of magnetic resonance diffusion tensor imaging (DTI) in evaluating cerebrovascular small vessel disease (CSVD) in patients with systemic lupus erythematosus (SLE).Methods:Eighty-two patients with SLE combined with CSVD treated at Yixing People's Hospital from January to December 2022 were selected. They were divided into acute phase infarction group (16 cases), chronic phase infarction group (26 cases), and chronic ischemic lesion group (40 cases) based on routine MRI examination results. All patients underwent DTI examination to obtain the average diffusion coefficient (DCavg) and anisotropy score (FA) of the affected and contralateral normal white matter areas, and the evaluation value of DTI for CSVD in SLE patients was analyzed.Results:The DCavg value on the affected side of 82 patients was significantly higher than that on the healthy side: (11.10 ± 3.48) 10 -3 mm 2/s vs. (8.18 ± 2.42) 10 -3 mm 2/s, and the FA value on the affected side was significantly lower than that on the healthy side: 0.28 ± 0.05 vs. 0.45 ± 0.08, with a statistical significant differences ( P<0.05). The DCavg values of the acute infarction group, chronic infarction group, and chronic ischemic focus group were (11.88 ± 3.50), (9.69 ± 3.24) and (8.52 ± 2.34) 10 -3 mm 2/s, respectively, with statistical significant differences ( P<0.05). The FA values of the acute infarction group, chronic infarction group, and chronic ischemic focus group were 0.28 ± 0.04, 0.33 ± 0.06 and 0.40 ± 0.07, respectively, with statistical significant differences ( P<0.05). The receiver operating characteristic curve was drawn, and the results showed that the area under the curve (AUC) of the acute phase infarction group and the chronic phase infarction group evaluated by DCavg and FA alone and in combination were 0.757, 0.756, and 0.820, respectively. The AUC of the chronic phase infarction group and the chronic ischemic focus group evaluated by DCavg and FA were 0.772, 0.776, and 0.813, respectively. The AUC value of the combined evaluation was relatively large. Conclusions:DTI has good evaluation value for CSVD in SLE patients and can accurately determine the type of CSVD.

Research progress on immunologic skin diseases in China / 中国免疫学杂志

Immunologic skin diseases encompass a spectrum of immune system-mediated autoimmune or inflammatory skin conditions,such as lupus erythematosus,psoriasis,atopic dermatitis,and vitiligo.Immunologic skin diseases are characterized by an unclear pathogenesis,complex disease processes,diverse clinical manifestations,and treatment difficulties,thereby presenting sig-nificant diagnostic and therapeutic challenges.Notably,Chinese researchers have achieved numerous innovative research findings on immunologic skin diseases in recent years.Over the past decade,Chinese scholars have contributed 11 919 SCI papers to the field of immune dermatosis,with more than 10 being published in the world's leading medical journals.These publications include one in Sci-ence,one in Nature,two in Cell,three in The New England Journal of Medicine,two in The Lancet,and one in Nature Medicine,as well as four in Immunity.Here,we aim to present a comprehensive summary of Chinese research progress pertaining to the pathogene-sis,diagnosis and treatment of immunologic skin diseases.