Assessment of depression, stress, anxiety and oral health-related quality of life in individuals with sjögren's syndrome: case control pilot study / Evaluación de la depresión, el estrés, la ansiedad y la calidad de vida relacionada con la salud bucal en personas con síndrome de Sjögren: estudio piloto de casos y controles

Objective: Sjögren's syndrome (SS) is a chronic auto-immune inflammatory systemic disease, in which the infiltration of mo-nonuclear cells in the exocrine glands leads to physiological and morphological changes. This pilot case-control study aims to describe the profile, evaluate the oral condition, quality of life (QoL) and psychological condition, through complete clinical examination, OHIP-14 and DASS-21 questionnaires. Materials and Methods: The study was conducted with seven individuals with a final diagnosis of SS (case group [CG]), and seven individuals with symptoms of dry mouth (control group [GCO]), consulting at the institution from January to November 2021. participants were selected by free demand and those previously seen at the institution with a diagnosis of SS between 19 and 70 years of age. The questionnaire OHIP-14 was applied to assess the patient's quality of life, where seven dimensions are assessed, subdivided into 14 questions through the Lickert scale (0 to 4) assigned by the individual and which quantifies the impact of oral health on QoL. The questionnaire DASS-21 assessed the psychological condition of the patient, which presents seven questions for each emotional state (depression, anxiety, and stress), totaling 21 questions. The general clinical condition, evolution of SS, oral clinical condition, and the profile of this population were related to QoL factors and psychological conditions, using these assessment instruments. Results: There was no statistically significant difference between the groups regarding stimulated salivary flow. The only symptom with a statistically significant difference in the CG was difficulty in phonation (p< 0.001). The dimensions related to functional limitation and physical pain showed the most expressive results (p=0.004) (p=0.025), showing a strong negative impact on the QoL of the CG individuals, and the dimension related to disability was the least affected (p=0.684). The analysis of depression, anxiety, and stress did not show statistically significant results between the groups; however, in the CG, 5 (71.42%) individuals showed a severe degree of depression, anxiety, and stress. Conclusions: Individuals in the case group showed some changes, with a strong negative impact on QoL compared to the control group.

Objetivo: El síndrome de Sjögren (SS) es una enfermedad inflamatoria sistémica crónica autoinmune, en la que la infiltración de células mononucleares en las glándulas exocrinas provoca cambios fisiológicos y morfológicos. Este estudio piloto de casos y controles tiene como objetivo describir el perfil, evaluar la condición bucal, calidad de vida (CdV) y condición psicológica, mediante examen clínico completo, cuestionarios OHIP-14 y DASS-21. Materiales y Métodos: El estudio se realizó con 7 individuos con diagnóstico final de SS, grupo de casos (CG) y 7 individuos con síntomas de sequedad bucal, grupo control (GCO) atendidos en la institución de enero a noviembre de 2021. Los participantes fueron seleccionados por libre demanda y entre los atendidos previamente en la institución con diagnóstico de SS entre 19 y 70 años de edad. Para evaluar la calidad de vida del paciente se aplicó el cuestionario OHIP-14, donde se evalúan siete dimensiones, sub-divididas en 14 preguntas a través de la escala de Likert (0 a 4) asignada por el individuo y que cuantifica el impacto de la salud bucal en la calidad de vida. El cuestionario DASS-21 evaluó la condición psicológica del paciente, el cual presenta siete preguntas para cada estado emocional (depresión, ansiedad y estrés), totalizando 21 preguntas. El estado clínico general, la evolución del SS, el estado clínico bucal y el perfil de esta población se relacionaron con factores de calidad de vida y condiciones psicológicas, mediante estos instrumentos de evaluación. Resultados: En cuanto al flujo salival estimulado, no hubo diferencias estadísticamente significativas entre los grupos. El único síntoma que mostró diferencia estadísticamente significativa en el CG fue la dificultad en la fonación (p< 0,001). Las dimensiones relacionadas con limitación funcional y dolor físico mostraron los resultados más expresivos (p=0,004) (p=0,025), mostrando un fuerte impacto negativo en la CdV de los individuos del GC, y la dimensión relacionada con discapacidad fue la menos afectada (p=0,684). El análisis de depresión, ansiedad y estrés no mostró resultados estadísticamente significativos entre los grupos; sin embargo, en el GC, 5 (71,42%) individuos presentaron un grado severo de depresión, ansiedad y estrés. Conclusión: Se puede concluir que los individuos del grupo de casos mostraron algunos cambios, con un fuerte impacto negativo en la calidad de vida en comparación con el grupo de control.

Sjögren's syndrome combined with cold agglutinin disease: A case report / 北京大学学报(医学版)

Sjögren's syndrome(SS)is a chronic autoimmune disease that affects exocrine glands, especially salivary and lacrimal glands. The main clinical manifestations are dry mouth and dry eyes, but also multi-organ and multi-system can be involved. Cold agglutinin disease(CAD)is an autoimmune disease characterized by red blood cell agglutination in the blood vessels of extremities caused by cold agglutinin at low temperature, resulting in skin microcirculation disturbance, or hemolytic anemia. Cold agglutinin disease is divided into two categories, primary cold agglutinin disease and secondary cold agglutinin disease. Primary cold agglutinin disease is characterized with cold agglutinin titer of 1 ∶4 000 or more and positive Coomb's test. However, the Coomb's test is not necessarily positive and the cold agglutinin titer is between 1 ∶32 and 1 ∶4 000 in secondary cold agglutinin disease. Here, we reported an elderly patient admitted to hospital due to fever. He was diagnosed with respiratory infection, but he showed incompletely response to the anti-infection treatment. Further laboratory tests showed the patient with positive ANA and anti-SSA antibodies. Additionally, the patient complained that he had dry mouth and dry eyes for 1 year. Schirmer test and salivate gland imaging finally confirmed the diagnosis Sjogren's syndrome. During the hospital stay, the blood clots were found in the anticoagulant tubes. Hemolytic anemia was considered as the patient had anemia with elevated reticulocytes and indirect bilirubin. In addition, further examination showed positive cold agglutination test with a titer of 1 ∶1 024, and cold agglutinin disease was an important type of cold-resistant autoimmune hemolytic anemia. Furthermore, the patient developed cyanosis after ice incubating at the tip of the nose. Hence, the patient was diagnosed as CAD and he was successfully treated with glucocorticoids instead of anti-infection treatments. Hence, the patient was diagnosed with SS combined with secondary CAD. SS combined CAD are rarely reported, and they are both autoimmune diseases. The abnormal function of B lymphocytes and the production of autoantibodies might be the common pathogenesis of them. Cold agglutinin disease can lead to severe hemolytic anemia, even life-threatening. In clinical practice, timely recognizing and dealing with CAD might promote the prognosis of the patient.

Pregnancy-associated neuromyelitis optical spectrum disorder combined with primary Sjögren's syndrome: A critical illness case report / 北京大学学报(医学版)

Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.

Clinical and immunological features of primary Sjögren's syndrome patients with positive anti-centromere protein B antibody / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical and immunological features of primary Sjögren's syndrome (pSS) patients with positive anti-centromere protein B (CENP-B) antibody.@*METHODS@#In this cross-sectional study, the general clinical data, radiographic examination and labial salivary gland biopsy data, and serum immunological and biochemical data of patients diagnosed with pSS from January 2016 to August 2022 were evaluated. The included patients were divided into the anti-CENP-B antibody positive and negative groups. Intergroup differences were analyzed with SPSS 23.0 software. Subgroup analysis was further performed by dividing the anti-CENP-B antibody positive group into the single anti-CENP-B antibody positive and with other auto-antibodies positive groups to determine the characters related to anti-CENP-B antibody.@*RESULTS@#In this study, 288 patients with pSS were evaluated, including 75 patients with anti-CENP-B antibody positive and 213 with anti-CENP-B antibody negative. Univariate analysis showed that compared with the anti-CENP-B antibody negative group, the patients of the anti-CENP-B antibody positive group were older, had lower proportion of the patients with salivary gland enlargement and higher proportion of autoimmune liver disease. As for immunological indicators, the positive proportions of anti-SSA/Ro60, anti-Ro52, and anti-SSB antibodies were significantly lower. Moreover, the immunoglobulin (Ig) G and rheumatoid factor levels were significantly lower, while the IgM level was significantly higher in the patients of the anti-CENP-B antibody positive group. As for serum biochemical indicators, for the patients of the anti-CENP-B antibody positive group, the level of total protein (TP) was lower, the albumin/globulin ratio was higher, and the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH) were higher. Subgroup analysis showed that the levels of TP and IgA in the patients of the single anti-CENP-B antibody positive group were significantly lower than those of the patients with other autoantibodies positive group.@*CONCLUSION@#The pSS patients with anti-CENP-B antibody positive have unique clinical and immunological features of lower disease activity, less likely to involve salivary gland, higher risk for autoimmune liver disease, and higher levels of liver function indicators. Anti-CENP-B antibody may be a marker for a distinct subset of polyautoimmunity in Sjögren's syndrome.

Clinical characteristics of fetal cardiac disease in patients with anti-SSA antibody positive / 北京大学学报(医学版)

OBJECTIVE@#To investigate the clinical manifestations and laboratory indicators of anti-Sjögren's-syndrome-related antigen A (SSA) antibody associated fetal cardiac disease.@*METHODS@#Pregnant women hospitalized at Peking University People's Hospital from January 2013 to July 2023 were included. Eleven patients with anti-SSA antibody positive were eventually diagnosed with fetal cardiac di-sease. And patients with anti-SSA antibody positive without fetal cardiac disease were selected as controls. Clinical manifestations, laboratory indications and drug usage were compared between the two groups.@*RESULTS@#Among these 11 patients, congenital heart block was confirmed in seven, which was the most common manifestations of fetal cardiac malformation. The proportion of the patients diagnosed with autoimmune disease before pregnancy in fetal cardiac malformation group was significantly lower than that in the control group (P=0.032), while most of the patients in the fetal cardiac malformation group received immune-related examinations for the first time because of this time's fetal cardiac diagnosis. While most of the patients in the control group received routine examinations because of autoimmune diseases diagnosed before pregnancy. During pregnancy, the white blood cell level [(9.29±2.58)×109/L vs. (7.10±1.90×109/L, t=3.052, P=0.004], erythrocyte sedimentation rate [(49.50 (48.00, 51.00) mm/h vs. 23.00 (15.00, 30.25) mm/h, Z=-2.251, P=0.024], IgA level [3.46 (2.30, 5.06) g/L vs. 2.13 (1.77, 2.77) g/L, Z=-2.181, P=0.029], and antinuclear antibody (ANA) titers [1∶320 (1∶160, 1∶320) vs. 1∶80 (1∶40, 1∶160), Z=-3.022, P=0.003] were significantly higher in fetal cardiac malformation group than in the control group. The proportion of positive anti-SSB antibody during pregnancy did not show a statistically significant difference between the two groups (37.5% vs. 7.7%, P=0.053). There was no significant difference in hydroxychloroquine dosage and initiation time between the two groups. The dosage of prednisone in the second and third trimesters was significantly higher in the cardiac malformation group than that in the control group, but there was no significant difference in the first trimester.@*CONCLUSION@#Fetal cardiac disease is rare in pregnant women with anti-SSA antibody. White blood cell, erythrocyte sedimentation rate, IgA, the titer of ANA positivity were higher in the fetal heart disease group during pregnancy. Since congenital heart block is difficult to reverse, its prevention and monitoring are more important than remedial treatment.

Early prediction of severe COVID-19 in patients with Sjögren's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19).@*METHODS@#We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection.@*RESULTS@#The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively.@*CONCLUSION@#PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.

Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody / 北京大学学报(医学版)

OBJECTIVE@#To analyze the differences of clinical manifestations and laboratory features between primary Sjögren's syndrome (pSS) patients with positive and negative anti-Sjögren's syndrome type B (SSB) antibody.@*METHODS@#The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology, Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups. The t test, Mann-Whitney U test, Chi-square test and Fisher's exact probability were used for analysis.@*RESULTS@#A total of 142 pSS patients were enrolled in this study, including 137 females and 5 males with a mean age of (54.8±13.3) years. The anti-SSB positive group included 44 patients accounting for 31.0% of the pSS patients. The anti-SSB positive pSS patients were younger at disease onset and at visit [age at visit: (50.9±14.5) years vs. (56.5±12.4) years; age at onset: (42.2±14.8) years vs. (49.5±15.3) years, P < 0.05]. The patients with anti-SSB positive more frequently presented with rash (29.5% vs. 14.3%, P < 0.05), enlargement of parotid glands (27.3% vs. 8.2%, P < 0.05), renal tubular acidosis (15.9% vs. 4.2%, P < 0.05), immune thrombocytopenia (9.1% vs. 1.0%, P < 0.05), rheumatoid factor (RF) positive (85.0% vs. 49.4%, P < 0.05), higher RF and antinuclear antibody (ANA) titers (median: 89.8 IU/mL vs. 20.5 IU/mL; median: 320 vs. 160, P < 0.05), anti-Sjögren's syndrome type A (SSA) antibody positive (97.7% vs. 64.3%, P < 0.05), elevation of γ globulin (71.4% vs. 38.5%, P < 0.05), higher levels of IgG (median: 21.0 g/L vs. 15.6 g/L, P < 0.05), higher proportions of CD3-CD19+ cells [(21.0±11.9)% vs. (13.7±9.6)%, P < 0.05] and lower proportions of CD3+ cells [(67.2±14.4)% vs. (76.6%±13.1)%, P < 0.05] than those negative. However, the anti-SSB positive group was less likely to show anti-mitochondrial antibodies (AMA)-M2 positivity (10.5% vs. 35.6%, P < 0.05). Glucocorticoids (90.9% vs. 73.5%, P < 0.05) and immunosuppressants (54.5% vs. 36.7%, P < 0.05) were more frequently used in anti-SSB positive pSS patients than those negative.@*CONCLUSION@#The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms, higher levels of other antibodies and activation of B cells than those negative. Glucocorticoids and immunosuppressants were more frequently used, indicating that anti-SSB positive group presented with a more severe clinal phenotype.

Clinical features of oral management to oral complications of Sjögren's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To understand the clinical characteristics about sequence diagnosis and treatment of oral complications in patients with Sjögren's syndrome (SS) through retrospective analysis, and to provide some guidance for clinical work.@*METHODS@#Some SS patients who underwent oral sequence management in the Department of General Dentistry, Peking University School and Hospital of Stomatology from January 2015 to September 2021 were enrolled. For the SS patients included in this study, a comprehensive oral examination was performed, including parotid region examination, oral mucosal exa-mination, dentition examination, dental examination, periodontal examination, unstimulated salivary flow rate, Candida infection and radiological imaging examination. According to the examination results, the patients were given fluoride application, antifungal treatment, root canal therapy, direct filling repair, and indirect repair treatment in sequence and the results recorded.@*RESULTS@#A total of 9 patients with SS, with 4 primary SS patients (pSS) and 5 secondary SS patients (sSS) were enrolled in the study. For all the 9 patients, the average age was (49.2±16.2) years and the median xerostomia duration 5 years. The unstimulated salivary flow rate of the 9 patients was all less than 1 mL/10 min. Eight of the 9 cases was diagnosed as oral Candidiasis, with positive salivary Candida culture result (>200 cfu/mL), and 1 of the 9 cases was not. The average decay, missing, filling teeth (DMFT) was 24.8±4.2; the average decay, missing, filling tooth surfaces (DMFS) was 59.2±21.9, the average incisal caries was 2.5±1.3, and the average number of crown restorations at baseline was 4.5±3.6. All the 9 SS patients were applied with topical fluoride usage, and 8 were prescribed with antifungal treatment. One sSS patient was conducted with filling restoration treatment, one pSS patient was conducted with full mouth rehabilitation, and the remaining 7 patients were conducted with direct filling combined with fixed repair treatment. The average 3.2 full crown restorations in 6 patients had to be removed and restored because of secondary caries, and 3 of the 9 patients underwent implant denture restorations finally.@*CONCLUSION@#Management of oral complications in SS patients needs to be carried out in sequence. A comprehensive examination and diagnosis should be carried out first, followed by infection control, and then restoration of oral function at last.

SHED-derived exosomes ameliorate hyposalivation caused by Sjögren's syndrome via Akt/GSK-3β/Slug-mediated ZO-1 expression / 中华医学杂志(英文版)

BACKGROUND@#Sjögren's syndrome (SS) is an autoimmune disorder characterized by sicca syndrome and/or systemic manifestations. The treatment is still challenging. This study aimed to explore the therapeutic role and mechanism of exosomes obtained from the supernatant of stem cells derived from human exfoliated deciduous teeth (SHED-exos) in sialadenitis caused by SS.@*METHODS@#SHED-exos were administered to the submandibular glands (SMGs) of 14-week-old non-obese diabetic (NOD) mice, an animal model of the clinical phase of SS, by local injection or intraductal infusion. The saliva flow rate was measured after pilocarpine intraperitoneal injection in 21-week-old NOD mice. Protein expression was examined by western blot analysis. Exosomal microRNA (miRNAs) were identified by microarray analysis. Paracellular permeability was evaluated by transepithelial electrical resistance measurement.@*RESULTS@#SHED-exos were injected into the SMG of NOD mice and increased saliva secretion. The injected SHED-exos were taken up by glandular epithelial cells, and further increased paracellular permeability mediated by zonula occluden-1 (ZO-1). A total of 180 exosomal miRNAs were identified from SHED-exos, and Kyoto Encyclopedia of Genes and Genomes analysis suggested that the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway might play an important role. SHED-exos treatment down-regulated phospho-Akt (p-Akt)/Akt, phospho-glycogen synthase kinase 3β (p-GSK-3β)/GSK-3β, and Slug expressions and up-regulated ZO-1 expression in SMGs and SMG-C6 cells. Both the increased ZO-1 expression and paracellular permeability induced by SHED-exos were abolished by insulin-like growth factor 1, a PI3K agonist. Slug bound to the ZO-1 promoter and suppressed its expression. For safer and more effective clinical application, SHED-exos were intraductally infused into the SMGs of NOD mice, and saliva secretion was increased and accompanied by decreased levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and Slug and increased ZO-1 expression.@*CONCLUSION@#Local application of SHED-exos in SMGs can ameliorate Sjögren syndrome-induced hyposalivation by increasing the paracellular permeability of glandular epithelial cells through Akt/GSK-3β/Slug pathway-mediated ZO-1 expression.

Analysis of adverse neonatal outcomes in pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies / 中华妇产科杂志

Objective: To investigate the relationship between positive anti-Ro/Sjögren syndrome antigen type A (SSA) antibody and anti-La/Sjögren syndrome antigen type B (SSB) antibody in pregnant women and neonatal adverse outcomes. Methods: This study was a retrospective study, and 145 deliveries of 136 anti-Ro/SSA and anti-La/SSB antibody positive pregnant women were selected who had prenatal examination and delivered in Peking University First Hospital from January 2017 to June 2022. According to whether adverse neonatal outcomes occurred, 145 deliveries were divided into adverse outcome group (26 cases) and no adverse outcome group (119 cases). According to the time when anti-Ro/SSA and anti-La/SSB antibodies were found positive, 145 deliveries were divided into the antibody positive during pregnancy group (69 cases) and the pre-pregnancy antibody positive group (76 cases). The pregnancy outcomes, treatment and maternal and infant antibody levels of pregnant women between the adverse outcome group and no adverse outcome group, between antibody positive during pregnancy group and the pre-pregnancy antibody positive group were compared. Results: (1) Most of the pregnant women with positive anti-Ro/SSA and anti-La/SSB antibodies were diagnosed as undifferentiated connective tissue disease, accounting for 40.4% (55/136), followed by Sjogren's syndrome (25.0%, 34/136), systemic lupus erythematosus (23.5%, 32/136), antiphospholipid antibody syndrome (6.6%, 9/136), idiopathic thrombocytopenic purpura (1.5%, 2/136), and 4 cases were not diagnosed. (2) The titers of anti-Ro/SSA and anti-La/SSB antibodies in the first trimester and the second trimester were compared, and there were no statistical significances (all P>0.05). (3) The proportion of high level anti-Ro/SSA antibody (>100 kU/L), positive level of anti-La/SSB antibody and positive rate of anti-La/SSB antibody in the adverse outcome group were higher than those in the no adverse outcome group, and the birth weight of newborns and live birth rate in the adverse outcome group were lower than that in the no adverse outcome group, all with statistical significances (all P<0.05). The anti-Ro/SSA antibody level, the proportion of drug treatment (hydroxychloroquine, glucocorticoid, gamma globulin), the incidence of fetal growth restriction (FGR), the rate of preterm birth, and the positive level of anti-Ro/SSA and anti-La/SSB antibodies in newborns were compared between the two groups, and there were no statistically significant differences (all P>0.05). (4) The anti-Ro/SSA antibody level of pregnant women in the pre-pregnancy antibody positive group, the proportion of hydroxychloroquine and glucocorticoid treatment, and the anti-Ro/SSA antibody positive rate of newborns were higher, while the incidence of FGR and gamma globulin treatment rate of newborns in the antibody positive during pregnancy group were higher, respectively, and the differences were statistically significant (all P<0.05). The levels of anti-La/SSB antibodies in pregnant women, anti-Ro/SSA and anti-La/SSB antibodies in newborns, the positive rate of anti-La/SSB antibodies in newborns and the incidence of adverse outcomes were compared between the antibody positive during pregnancy group and the pre-pregnancy antibody positive group, and there were no statistical significances (all P>0.05). Conclusions: High concentrations of anti-Ro/SSA antibodies and co-positive anti-La/SSB antibodies during pregnancy may increase the incidence of adverse neonatal outcomes. There is no significant difference in the incidence of adverse neonatal outcomes between antibody positive pregnant women and antibody positive pregnant women who were first found during pregnancy after comprehensive treatment in the rheumatology and immunology department.

Research progress in treatment of Sjögren's syndrome by traditional Chinese medicine / 中国中药杂志

Sj9gren's syndrome(SS) is an autoimmune disease with glandular dysfunction caused by the massive infiltration of the exocrine glands by lymphocytes. The pathogenesis of this disease is related to the chronic inflammatory response of the exocrine glands due to excessive activation of B cells and T cells. In addition to dry mouth and eyes, SS can also cause damage to other organs and systems in the human body, seriously affecting the quality of life of patients. Traditional Chinese medicine(TCM) has definite clinical efficacy in the treatment of SS as it can alleviate symptoms and regulate immune disorders without causing adverse reactions, demonstrating high safety. This paper reviews the current status of preclinical and clinical trials about the TCM treatment of SS in the past decade. TCM mainly mitigates SS symptoms such as dry mouth, dry eyes, dry skin, and joint pain and improves the prognosis and quality of life of patients by regulating the abnormally activated B cells and T cells, inhibiting the autoimmune response, restoring the balance between pro-inflammatory and anti-inflammatory cytokines, and reducing the pathological damage caused by immune complexes to exocrine glands and joints in SS patients.

Sjögren's syndrome: Epidemiology and clinical manifestations

Sjögren's syndrome is an entity of rheumatic origin, with complex autoimmune characteristics, in which the salivary and lacrimal glands are mainly compromised. It has two forms of presentation, one primary and the other secondary, and in both forms there is evidence of exocrine glands involvement. The clinical spectrum of Sjögren's syndrome is very heterogeneous and is classified into glandular and extra-glandular manifestations, but not mutually exclusive. It is recommended that all patients with parotid inflammation, purpura, hypergammaglobulinaemia, anti-SSa, and anti-SSb should be seen to have a greater risk of presenting with a severe systemic presentation, and it is recommended to carry out a more strict medical control. Population studies that have attempted to describe the incidence and prevalence of Sjögren's syndrome in various countries throughout the world are to some extent discordant between one registry and another. Although Sjögren's syndrome is more common in women, ocular involvement predominates in men, and it can occur in all ages, mainly between the third and fifth decades of life. In children it is rare. It is also considered as a common connective tissue disease, where the data on the global incidence rate and prevalence are underestimated.

El síndrome de Sjögren es una entidad de origen reumático, con características autoinmune complejas, en la que se ven comprometidas principalmente las glándulas salivales y las lagrimales. Tiene 2 formas de presentación, una primaria y otra secundaria, y en ambas se observa una afección de las glándulas exocrinas. El espectro clínico del síndrome de Sjögren es muy heterogéneo y se clasifica en manifestaciones glandulares y extraglandulares, no excluyentes entre sí. Se recomienda que se haga un control médico más estricto a todo paciente que curse con una inflamación parotídea, púrpura, hipergammaglobulinemia y anticuerpos anti-SSa, anti-SSb, puesto que presenta mayor riesgo de cursar con una presentación sistémica grave. Los estudios poblacionales que han intentado describir la incidencia y la prevalencia del síndrome de Sjögren en diferentes países son hasta cierto punto discordantes entre un registro y otro. El síndrome de Sjögren es más frecuente en mujeres, pero en hombres predomina más la afectación ocular; puede presentarse en todas las edades, principalmente entre la tercera y la quinta décadas de la vida; en niños es raro. Se considera además como una conectivopatía frecuente, en la cual los datos de la tasa de incidencia global y de prevalencia se encuentran subestimados.

ANCA vasculitis and membranoproliferative glomerulonephritis associated with Sjögren's syndrome: Case report and literature review

ANCA-associated vasculitis may occur concomitantly with primary Sjögren's syndrome (SS) or arise during its evolution. We present the case of a patient who underwent dry symptoms, a positive Schirmer test and an SS-compatible autoimmunity profile and, simultaneously, deterioration of renal function, anaemia, and dyspnoea, requiring renal biopsy and fibro-bronchoscopy. Complementary studies documented acute necrotizing glomerulonephritis with extracapillary proliferation, and membranoproliferative pattern with immune complex deposition. Bronchoalveolar lavage was compatible with alveolar haemorrhage. Kidney lung syndrome secondary to ANCA vasculitis was diagnosed and treatment with steroid and intravenous cyclophosphamide with clinical and paraclinical improvement was instituted. Mixed renal involvement found in this case is uncommon in patients with SS, and treatment changes significantly, hence the importance of differential diagnosis and reporting in the literature.

La vasculitis asociada con anticuerpos anticitoplasma de neutrófilos-ANCA puede presentarse concomitantemente con síndrome de Sjögren primario o surgir durante su evolución. Se presenta el caso de una paciente que cursó con síntomas secos, test de Schirmer positivo, perfil de autoinmunidad compatible con síndrome de Sjögren y, de forma simultánea, deterioro de la función renal, anemia y disnea, por lo que requirió biopsia renal y fibrobroncoscopia. Los estudios complementarios documentaron glomerulonefritis aguda necrosante con proliferación extracapilar y patrón membranoproliferativo con depósito de complejos inmunes. El lavado broncoalveolar fue compatible con hemorragia alveolar. Se hizo diagnóstico de síndrome de pulmón-rinón secundario a vasculitis ANCA y se instauró tratamiento con esteroide y ciclofosfamida intravenosa, con mejoría clínica y paraclínica. El compromiso renal mixto encontrado en este caso es infrecuente en pacientes con SS, y el tratamiento cambia ostensiblemente, de ahí la importancia del diagnóstico diferencial y el reporte en la literatura.

Utilidad de la proteína C reactiva en el posoperatorio inmediato de un paciente reumático con apendicitis aguda / Usefulness of C-reactive protein in the immediate postoperative period of rheumatic patients with acute appendicitis

Las enfermedades reumáticas son un grupo de afecciones que se caracterizan por la presencia de manifestaciones y complicaciones sistémicas derivadas del proceso inflamatorio mantenido. Los reactantes de fase aguda, como es el caso de la proteína C reactiva constituyen un marcador de actividad de la enfermedad. Sin embargo, su utilidad se magnifica en los pacientes reumáticos que tienen que ser sometidos a una intervención quirúrgica, circunstancia en la que se tornan un marcador eficiente que muestra la magnitud del proceso inflamatorio. Se presenta el caso de una paciente femenina de 53 años edad, con diagnóstico de artritis reumatoide y síndrome de Sjögren secundario, que tuvo que ser sometida a intervención quirúrgica por diagnóstico de apendicitis aguda. Se realizó seguimiento clínico y de laboratorio utilizando la proteína C reactiva como marcador de elección para monitorear la intensidad del proceso inflamatorio resultante de la intervención quirúrgica y de los efectos de esta en la actividad clínica de las enfermedades reumáticas de base. Después del tratamiento quirúrgico y medicamentoso, la paciente fue dada de alta hospitalaria sin manifestaciones articulares, digestivas ni alteraciones de los exámenes de laboratorio(AU)

Rheumatic diseases are a group of conditions characterized by the presence of systemic manifestations and complications derived from the sustained inflammatory process. Acute phase reactants, such as C-reactive protein, constitute a marker of disease activity. However, its usefulness is magnified in those rheumatic patients who have to undergo surgery, being an efficient marker that shows the magnitude of the inflammatory process. We present the case of a 53-year-old female patient diagnosed with rheumatoid arthritis and secondary Sjögren's syndrome who had to undergo surgery due to a diagnosis of acute appendicitis. Clinical and laboratory follow-up was performed using C-reactive protein as the marker of choice to monitor the intensity of the inflammatory process resulting from the surgical intervention and its effects on the clinical activity of underlying rheumatic diseases(AU)

Systemic autoimmune diseases and work outcomes in Brazil: a scoping review

ABSTRACT OBJECTIVE To review articles that assessed work-related outcomes such as workability, work productivity, presenteeism, absenteeism, sick leave, return to work, and employment status of Brazilian patients with rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, and systemic autoimmune myopathies. METHODS This study was conducted in Medline databases (PubMed), SciELO, and Lilacs through a combination of descriptors of interest. Studies published until December 2020 were considered in the search strategy. RESULTS Eight out of 90 articles met the eligibility criteria and were included in this review. The studies are highly heterogeneous. Most of them are cross-sectional, and all of them address rheumatoid arthritis or systemic lupus erythematosus. A common denominator among these studies is the high proportion of patients outside the labor market. CONCLUSIONS In general, the studies show unfavorable labor outcomes and impaired participation in the Brazilian workforce among the samples of patients assessed. There is a need to better understand several topics about Brazilian patients with systemic autoimmune diseases and their work context, as well as to conduct studies focusing on rarer diseases and on the themes of return and reintegration to work.

Long-term follow-up of a case of choroidal neovascularization secondary to reticular pigmentary retinal dystrophy / Seguimento de longo-prazo de um caso de neovascularização de coroide secundária à distrofia reticular pigmentar da retina

ABSTRACT Reticular pigmentary retinal dystrophy, also known as Sjögren's reticular dystrophy, is a rare condition characterized by macular lesions with a reticular pattern, which are best seen on fluorescein angiogram. Choroidal neovascularization secondary to this type of dystrophy is even less common. This report describes a case of reticular pigmentary retinal dystrophy with vision loss due to neovascular membrane, which responded well to treatment with anti-vascular endothelial growth factor.

RESUMO A distrofia reticular pigmentar da retina, também conhecida como distrofia reticular de Sjögren, é uma doença rara, caracterizada por lesões maculares com um padrão reticular, que são mais bem visualizadas na angiografia com fluoresceína. A neovascularização de coroide secundária a este tipo de distrofia é ainda menos comum. Este relato descreve um caso de distrofia reticular pigmentar da retina, com perda de visão devido à membrana neovascular, que respondeu bem ao tratamento com fator de crescimento endotelial antivascular.

Subconjunctival adalimumab for treatment of dry eye disease in Sjögren's syndrome / Tratamento de olho seco com adalimumabe subconjuntival em pacientes portadores da síndrome de Sjögren

ABSTRACT Objective To describe the use of subconjuctival administration of the anti-tumor necrosis factor agent adalimumab for treatment of dry eye in patients with Sjögren's syndrome, and to investigate conjunctival healing. Methods Prospective, nonrandomized, noncomparative interventional case series including consecutive patients with Sjögren's syndrome and dry eye disease treated with subconjunctival adalimumab, who were refractory to conventional treatment. Patients with infectious ocular surface involvement or structural changes in the tear pathway or eyelids were excluded. Data recorded included age, sex, lissamine green staining pattern, Schirmer test results, intraocular pressure, conjunctival mobility, tear break up time and findings of biomicroscopic evaluation, following fluorescein dye instillation. The Ocular Surface Disease Index questionnaire validated for the Portuguese language was used for subjective assessment of patients. Results Eleven eyes of eight patients were studied. Mean patient age was 53±13.4 years. Patients were treated with subconjunctival injection of 0.03 mL of adalimumab and followed for 90 days thereafter. There were no statistically significant objective improvement (objective tests results; p>0.05) and no statistically significant changes in intraocular pressure (p=0.11). Questionnaire responses revealed a significant improvement in ocular symptoms (p=0.002). Conclusion Based on the Ocular Surface Disease Index questionnaire, subconjunctival administration of adalimumab improved dry eye symptoms. However, objective assessments failed to reveal statistically significant improvements.

RESUMO Objetivo Descrever o uso subconjuntival do antifator de necrose tumoral adalimumabe para o tratamento do olho seco em pacientes com síndrome de Sjögren e avaliar a cicatrização conjuntival. Métodos Série de casos intervencionista com desenho prospectivo, não randomizado, não comparativo. O medicamento adalimumabe foi aplicado em região subconjuntival em pacientes com síndrome de Sjögren e olho seco que eram resistentes a outras terapias convencionais. Pacientes com patologias oculares de origem infecciosa ou com alterações estruturais nas vias lacrimais e pálpebras foram excluídos do estudo. Os dados coletados incluíram idade, sexo, teste com lisamina verde, teste de Schirmer, pressão intraocular, mobilidade conjuntival, teste de ruptura do filme lacrimal, e avaliação biomicroscópica com colírio de fluoresceína. Além disso, o questionário Ocular Surface Disease Index validado para a língua portuguesa foi aplicado com objetivo de avaliar subjetivamente a resposta dos pacientes ao tratamento. Resultados Onze olhos de oito pacientes foram estudados. A idade média dos pacientes foi de 53±13,4 anos. A dose aplicada de adalimumabe subconjuntival foi de 0,03mL, e a duração do seguimento foi de 90 dias após a injeção. Não houve melhora estatisticamente significativa nos testes objetivos (todos apresentaram p>0,05). A pressão intraocular também não sofreu variações estatisticamente significativas (p=0,11). Entretanto, por meio do questionário, foi registrada melhora significativa dos sintomas oculares (p=0,002). Conclusão O uso do adalimumabe subconjuntival melhorou os sintomas de olho seco, avaliados por meio do questionário Ocular Surface Disease Index, mas não houve melhora estatisticamente significativa na avaliação objetiva.

Tumor de Klatskin en una paciente con diagnóstico de síndrome de Sjögren / Klatskin tumor in a patient diagnosed with Sjögren's syndrome

El proceso inflamatorio crónico de las enfermedades reumáticas constituye un factor que causa afectación en otros órganos y sistemas de órganos. La afectación puede llegar a producir metaplasia de la mucosa de distintos tejidos y condicionar la aparición de enfermedades neoplásicas. Los pacientes con síndrome de Sjögren tienen un 40 por ciento de aumento de riesgo de padecer una enfermedad tumoral con respecto a los pacientes sanos o con otras enfermedades crónicas no inflamatorias. El objetivo del presente estudio es dar a conocer las características clínico-imagenológicas que posibilitaron el diagnóstico de un tumor de Klatskin en una paciente femenina de 57 años de edad con antecedentes de 5 años de evolución del síndrome de Sjögren. Se realizó una colangiopancreatografía retrógrada endoscópica para eliminar el tumor. A los tres días de la intervención quirúrgicamente la paciente muestra una evolución favorable por lo que se decide dar alta hospitalaria con seguimiento por consulta externa de especialidades de cirugía general y reumatología indistintamente. Durante todo el procedimiento se mantuvo el tratamiento para la enfermedad de base de la paciente. Actualmente la paciente se encuentra incorporada a sus actividades cotidianas y con una evolución favorable de su estado de salud(AU)

The chronic inflammatory process of rheumatic diseases constitutes a factor that causes affectation in other organs and organ systems. The affectation can produce metaplasia of the mucosa of different tissues and condition the appearance of neoplastic diseases. Patients with Sjögren's syndrome have a 40 percent increased risk of developing a tumor disease compared to healthy patients or other non-inflammatory chronic diseases. The objective of this study is to present the clinical-imaging characteristics that made the diagnosis of a Klatskin tumor possible in a 57-year-old female patient with a 5-year history of Sjögren's syndrome. Endoscopic retrograde cholangiopancreatography was performed to remove the tumor. Three days after the surgical intervention, the patient showed a favorable evolution, so it was decided to discharge from the hospital with follow-up by outpatient consultation of specialties of general surgery and rheumatology indistinctly. Treatment for the patient's underlying disease was maintained throughout the procedure. Currently the patient is incorporated into her daily activities and with a favorable evolution of her state of health(AU)

Reativação da BCG após vacina contra COVID-19: relato de caso / BCG reactivation after COVID-19 vaccine: case report

A reativação da BCG pode ocorrer em diversos contextos: associada a quadros infecciosos, imunossupressão, autoimunidade e pós-vacinações. Além disso, especialmente em crianças abaixo de 5 anos de idade, deve ser valorizada como um achando presente em cerca de 50% dos casos de Doença de Kawasaki. Neste artigo, relatamos o primeiro caso publicado na literatura de uma paciente adulta jovem, a qual manifestou uma reativação de BCG após receber a primeira dose de vacina contra COVID-19 (AztraZeneca/Oxford/Biomanguinhos). Dentro das primeiras 24h após a administração da vacina, a paciente desenvolveu febre alta, sudorese, dor local, mialgia difusa e cefaleia. Após dois dias, iniciou eritema e enduração no local da cicatriz da vacina BCG. Ela tem como comorbidade a urticária crônica espontânea, porém estava assintomática sem crises há mais de 1 ano. Tem como antecedente familiar relevante o óbito materno por síndrome complexa de sobreposição de autoimunidade (lúpus eritematoso sistêmico, síndrome de Sjögren e síndrome do anticorpo antifosfolípide). Após ser medicada com anti-inflamatórios não esteroides (AINE) e corticoterapia tópica de moderada potência por 3 dias, houve resolução completa da reativação da BCG. A paciente, após 3 meses, recebeu a segunda dose da vacina e não manifestou nenhum sintoma. Acredita-se que a reativação da BCG ocorra devido a um mecanismo de reação cruzada entre HSP do indivíduo, elicitadas como mediadores da imunidade inata frente à inflamação vacinal, com alguns epítopos do M. bovis. Recomendase que seja investigada alguma condição imunossupressora ou autoimune nos pacientes que manifestem reativação da BCG, principalmente em adultos, na qual a doença de Kawasaki é bastante rara. As vacinas, incluindo as contra COVID-19, também podem desencadear o surgimento deste fenômeno imunológico ainda pouco compreendido.

BCG reactivation can occur in different contexts: associated with infectious conditions, immunosuppression, autoimmunity and post-vaccinations. Also, especially in children below of 5 years of age, should be valued as a finding present in about 50% of cases of Kawasaki disease. In this article, we report the first case published in the literature of a young adult patient, who manifested a reactivation of BCG after receiving the first dose of vaccine against COVID-19 (AztraZeneca/Oxford/Biomanguinhos). Within the first 24 hours after the administration of the vaccine, the patient developed high fever, sweating, local pain, diffuse myalgia and headache. After 2 days, erythema and induration at the site of the BCG vaccine scar began. she has how comorbidity to chronic spontaneous urticaria, but she was asymptomatic without crises for more than 1 year. The relevant family history is maternal death due to the complex syndrome of autoimmunity overlap (systemic lupus erythematosus, Sjögrens syndrome, and anti-phospholipid antibody). After being medicated with NSAID and moderate topical corticosteroid therapy potency for 3 days, there was complete resolution of BCG reactivation. The patient, after 3 months, received the 2nd dose of the vaccine and had no symptoms. It is believed that the reactivation of BCG occurs due to a cross-reaction mechanism between the individuals HSP, elicited as mediators of innate immunity against vaccine inflammation, with some epitopes of M. bovis. It is recommended that any immunosuppressive or autoimmune condition be investigated in patients that manifest BCG reactivation, especially in adults, in which Kawasaki disease is quite rare. Vaccines, including those against COVID-19, can also trigger of this immunological phenomenon still poorly understood.

Submaxilitis aguda bilateral asociada con listeriosis en un paciente inmunodeprimido / Acute bilateral submaxillitis associated to listeriosis in immunosuppressed patient

Acute bilateral submaxillitis is a rare event, except when it is caused by sialolithiasis. It has been described secondary to allergic, infectious, suppurative or viral processes, autoimmune such as Sjögren's syndrome, drugs such as thiopurines, nitrofurantoin, phenylbutazone, captopril, and after upper airway procedures such as upper endoscopy, orotracheal intubation bronchoscopy and ERCP (endoscopic retrograde cholangiopancreatography for choledocholithiasis). Treatment with tumour necrosis factor-alpha (TNF-alpha) antagonist drugs is associated with an increased risk of reactivation of intracellular bacterial infections, so that listeriosis has been described in pathologies that require such treatment, such as rheumatic, dermatological and intestinal diseases, which present other comorbidities or are immunocompromised. Listeriosis mainly causes bacteremia and meningitis, when symptomatic, and infects immunosuppressed persons, where it has a lethality despite 30% antibiotherapy. We present the clinical case of a male immunosuppressed patient, secondary to a treatment with azathioprine and prednisone followed by adalimumab, for indeterminate inflammatory bowel disease, superinfected by CMV, who after eating meat contaminated by Listeria monocytogenes, suffered a picture of listeriosis bacteremia, which improved with antibiotic treatment, followed by a transient acute bilateral submaxillitis, which subsided with symptomatic treatment (oral hydration). It is the only case described in the literature, in which an immunosuppressed patient treated with adalimumab, suffers from acute bilateral submaxillitis in the context of listeriosis, caused by the mumps virus.

La submaxilitis aguda bilateral es un evento raro, salvo cuando está causada por sialolitiasis. Se la ha descrito secundaria a procesos alérgicos, infecciosos, supurativos, virales o autoinmunes como el síndrome de Sjögren; a la administración de fármacos como tiopurinas, nitrofurantoina, fenilbutazona, captopril, y tras procedimientos sobre la vía aérea superior, como endoscopia digestiva alta, broncoscopia, intubación orotraqueal y colangiopancreatografía retrógrada endoscópica por coledocolitiasis (CPRE). El tratamiento con fármacos antagonistas del factor de necrosis tumoral alfa (TNF-alfa) se asocia con riesgo acentuado de reactivación de infecciones bacterianas intracelulares, de forma que se ha descrito la listeriosis en afecciones que requieren dicho tratamiento, como enfermedades reumáticas, dermatológicas y del intestino en sujetos que presentaban otras comorbilidades o estaban inmunocomprometidos. La listeriosis provoca bacteriemia y meningitis predominantemente, cuando es sintomática, e infecta a los sujetos inmunodeprimidos, en los que, a pesar de la antibioticoterapia, tiene una letalidad del 30%. Se presenta el caso clínico de un paciente varón, inmunodeprimido, secundario a tratamiento por azatioprina y prednisona seguido de adalimumab, por enfermedad inflamatoria intestinal indeterminada, sobreinfectada por citomegalovirus, que tras la ingesta de carne contaminada por Listeria monocytogenes, sufrió un cuadro de bacteriemia por listeriosis que mejoró con tratamiento con antibióticos, seguido de submaxilitis aguda bilateral transitoria, que cedió con tratamiento sintomático (hidratación oral). Es el único caso descrito en la literatura en el que un paciente inmunodeprimido tratado con adalimumab presenta submaxilitis aguda bilateral en el contexto de la listeriosis, provocada por el virus de la parotiditis.