Physicochemical and microbiological stability study of two new preservative-free methylprednisolone eye drops. / Estudio de estabilidad fisicoquímica y microbiológica de dos nuevos colirios de metilprednisolona sin conservantes.

OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 mg/ml and 10 mg/ml eye drops for use in ocular pathologies such as Sjögren's syndrome and dry eye syndrome. METHOD: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5 ±3 °C), at room temperature (25 ± 2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones. RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/ml eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/ml eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/ml, presented a white precipitate from day 14 and 28 respectively. Non-refrigerated 1 mg/ml eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers. CONCLUSIONS: 1 mg/ml MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/ml eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.

Characterisation of macrophage infiltration and polarisation based on integrated transcriptomic and histological analyses in Primary Sjögren's syndrome.

Background: Primary Sjögren's syndrome (pSS) is a progressive inflammatory autoimmune disease. Immune cell infiltration into glandular lobules and ducts and glandular destruction are the pathophysiological hallmarks of pSS. Macrophages are one of the most important cells involved in the induction and regulation of an inflammatory microenvironment. Although studies have reported that an abnormal tissue microenvironment alters the metabolic reprogramming and polarisation status of macrophages, the mechanisms driving macrophage infiltration and polarisation in pSS remain unclear. Methods: Immune cell subsets were characterised using the single-cell RNA sequencing (scRNA-seq) data of peripheral blood mononuclear cells (PBMCs) from patients with pSS (n = 5) and healthy individuals (n = 5) in a public dataset. To evaluate macrophage infiltration and polarisation in target tissues, labial salivary gland biopsy tissues were subjected to histological staining and bulk RNA-seq (pSS samples, n = 24; non-pSS samples, n = 12). RNA-seq data were analysed for the construction of macrophage co-expression modules, enrichment of biological processes and deconvolution-based screening of immune cell types. Results: Detailed mapping of PBMCs using scRNA-seq revealed five major immune cell subsets in pSS, namely, T cells, B cells, natural killer (NK) cells, dendritic cells (DCs) and monocyte-macrophages. The monocyte-macrophage subset was large and had strong inflammatory gene signatures. This subset was found to play an important role in the generation of reactive oxygen species and communicate with other innate and adaptive immune cells. Histological staining revealed that the number of tissue-resident macrophages was high in damaged glandular tissues, with the cells persistently surrounding the tissues. Analysis of RNA-seq data using multiple algorithms demonstrated that the high abundance of pro-inflammatory M1 macrophages was accompanied by the high abundance of other infiltrating immune cells, senescence-associated secretory phenotype and evident metabolic reprogramming. Conclusion: Macrophages are among the most abundant innate immune cells in PBMCs and glandular tissues in patients with pSS. A bidirectional relationship exists between macrophage polarisation and the inflammatory microenvironment, which may serve as a therapeutic target for pSS.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with Sjögren`s syndrome in a child.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nervous system disease associated with polyautoimmunity. CASE: We report a previously healthy 13-year old boy who was referred to our outpatient clinic with gait disturbance and distal lower limb weakness that had been increasing for six months. The patient had decreased deep tendon reflexes in the upper extremities and absence in the lower extremities, reduced muscle strength in the distal and proximal lower extremities, muscle atrophy, drop foot, and normal pinprick sensations. The patient was diagnosed with CIDP as a result of clinical findings and electrophysiological studies. Autoimmune diseases and infectious agents were investigated in terms of triggering CIDP. Although there was no clinical sign other than polyneuropathy, he was also diagnosed with Sjögren`s syndrome due to positive antinuclear antibodies and antibodies against Ro52, and with autoimmune sialadenitis. After six months of monthly intravenous immunoglobulin and oral methylprednisolone treatments, the patient was able to dorsiflex his left foot and walk without support. CONCLUSIONS: To our knowledge, our case is the first pediatric case with the coexistence of Sjögren`s syndrome and CIDP. Therefore, we suggest investigating children with CIDP in terms of underlying autoimmune diseases such as Sjögren`s syndrome.

Emerging of a new CD3+CD31HCD184+ tang cell phenothype in Sjögren's syndrome induced by microencapsulated human umbilical cord matrix-derived multipotent stromal cells.

Background: Sjögren's syndrome (SS) is an autoimmune disease hallmarked by infiltration and destruction of exocrine glands. Currently, there is no therapy that warrants full recovery of the affected tissues. Umbilical cord-derived multipotent stromal cells, microincapsulated in an endotoxin-free alginate gel (CpS-hUCMS), were shown to modulate the inflammatory activity of PBMCs in SS patients in vitro, through release of soluble factors (TGFß1, IDO1, IL6, PGE2, VEGF). These observations led us to set up the present study, aimed at defining the in vitro effects of CpS-hUCMS on pro- and anti-inflammatory lymphocyte subsets involved in the pathogenesis of SS. Methods and results: Peripheral blood mononuclear cells (PBMCs) upon collection from SS patients and matched healthy donors, were placed in co-culture with CpS-hUCMS for five days. Cellular proliferation and T- (Tang, Treg) and B- (Breg, CD19+) lymphocyte subsets were studied by flow cytometry, while Multiplex, Real-Time PCR, and Western Blotting techniques were employed for the analysis of transcriptome and secretome. IFNγ pre-treated hUCMS were assessed with a viability assay and Western Blotting analysis before co-culture. After five days co-culture, CpS-hUCMS induced multiple effects on PBMCs, with special regard to decrease of lymphocyte proliferation, increase of regulatory B cells and induction of an angiogenic T cell population with high expression of the surface marker CD31, that had never been described before in the literature. Conclusion: We preliminarily showed that CpS-hUCMS can influence multiple pro- and anti-inflammatory pathways that are deranged in SS. In particular, Breg raised and a new Tang phenothype CD3+CD31HCD184+ emerged. These results may considerably expand our knowledge on multipotent stromal cell properties and may open new therapeutic avenues for the management of this disease, by designing ad hoc clinical studies.

Atypical posterior reversible encephalopathy syndrome associated with Sjögren'|s syndrome: a case report.

Sjögren'|s syndrome (SJS) is a common autoimmune disease. Generally, posterior reversible encephalopathy syndrome (PRES) is often concomitant with autoimmune disease; however, PRES rarely complicates SJS. Thus, the detailed clinical course of cases with SJS and PRES remains unknown. We present the case of a 71-year-old female patient with primary SJS, whose magnetic resonance (MR) images showed bilateral vasogenic edema in the basal ganglia, brainstem, and cerebellum. Cerebrospinal fluid (CSF) examination revealed increased IgG index and higher interleukin-6 and anti-SSA-autoantibody levels. Management of her blood pressure combined with corticosteroid therapy improved her neurological symptoms, including abnormal CSF and MR imaging findings.

Insights Gained and Future Outlook From scRNAseq Studies in Autoimmune Rheumatic Diseases.

Autoimmune rheumatic diseases have a major impact on public health as one of the most common morbidities, and many of these disorders involve both local and systemic manifestations with severe consequences for patient health and quality of life. However, treatment options for many of these diseases remain inadequate for a substantial portion of patients, and progress in developing novel therapeutics has been slow. This lack of progress can be largely attributed to an insufficient understanding of the complex mechanisms driving pathogenesis. Recently, the emergence of single-cell RNA sequencing (scRNAseq) has offered a powerful new tool for interrogating rheumatic diseases, with the potential to assess biological heterogeneity and individual cell function in rheumatic diseases. In this review, we discuss the major insights gained from current scRNAseq interrogations of human rheumatic diseases. We highlight novel cell populations and key molecular signatures uncovered, and also raise a number of hypotheses for follow-up study that may be of interest to the field. We also provide an outlook into two emerging single-cell technologies (repertoire sequencing and spatial transcriptomics) that have yet to be utilized in the field of rheumatic diseases, but which offer immense potential in expanding our understanding of immune and stromal cell behavior. We hope that scRNAseq may serve as a wellspring for the generation and interrogation of novel hypotheses regarding autoreactive lymphocytes and tissue infiltration patterns, and help uncover novel avenues for therapeutic development.

Cardiovascular Effect of Physical Exercise on Primary Sjogren's Syndrome (pSS): Randomized Trial.

Objective: To evaluate the effects of an exercise program on aerobic capacity, echocardiographic parameters, metabolic profile, quality of life and safety in patients with primary Sjogren's syndrome in a randomized trial. Methods: 60 women with pSS were evaluated from the SF-36 Short-Form Health Survey (SF-36) and EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) questionnaires. The participants performed ergospirometry and echocardiography; blood samples were collected to evaluate the metabolic profile. Patients were randomly divided into 2 groups: a training group that participated in the supervised training program and a control group. All variables were analyzed at baseline and after 28 weeks for both groups and we performed an intention-to-treat analysis. The training program consisted of 16 weeks of resistance exercises and, after, the exercise became aerobic. Patients and coaches were not blinded, contrary to the evaluators of all examinations/procedures and data analysts. Statistical analysis included Wilcoxon's rank sum test, chi-square test, and ANOVA test. P values < 0.05 were considered to be statistically significant. Results: The 2 groups were homogeneous at baseline. The training group showed a significant improvement in oxygen maximum volume (VO2max) and anaerobic threshold (AT). Comparison of the training group and control group after 28 weeks showed a significant difference relating to VO2max and in AT. We did not find statistically significant diference in echocardiographic parameters, metabolic profile and in questionnaires SF-36 and ESSDAI. Conclusions: This study showed significant improvement in aerobic capacity and glycated hemoglobin after a supervised training program in patients with pSS with safety.

Identification of the key genes and pathways involved in B cells in primary Sjögren' s syndrome.

Primary Sjögren' s syndrome (pSS) is a relatively common autoimmune disease, which mainly involves the exocrine glands, causing dry eye, dryness of mouth, fatigue and pain in the joints, thus severely affecting the normal lives of patients. B cell populations are considered to play an important role in their pathogenesis and pSS patients are generally characterized by exhibiting biological signs of B cell activation. Moreover, another important characterized change in the peripheral blood of pSS patients is found to be the decreased number of circulating memory B cells. However, the mechanisms underlying the B cell activation and the decreased level of circulating memory B cells in pSS patients are still unclear. Therefore, we identified key genes and pathways involved in B cells in pSS through a combination of several bioinformatic approaches including Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and weighted gene co-expression network analysis (WGCNA) using gene expression data of pSS patients and controls from an open database Gene Expression Omnibus (GEO). The results may provide some novel insights into the pathogenesis of pSS. Moreover, we constructed and validated a diagnostic model for pSS by using the expression patterns of these key genes, which may assist clinicians in diagnosing pSS.

Ankylosing spondylitis coexists with rheumatoid arthritis and Sjögren's syndrome: a case report with literature review.

Rheumatoid arthritis (RA), ankylosing spondylitis (AS), and Sjögren's syndrome (SS) are the most common rheumatic diseases. However, a coexistence of AS and RA or SS in the same patient is rare. What' s more, the case of AS coexists with RA, and SS is not be found yet. Here, we present a 65-year-old male patient who develop typical clinical symptoms of AS, RA, and SS successively (such as inflammatory low back pain, symmetrical small joint swelling and pain, and severe dryness of mouth and eyes) and was finally diagnosed with AS coexisting with RA and SS.

Neurofilament light is a biomarker of brain involvement in lupus and primary Sjögren's syndrome.

BACKGROUND: To test the hypothesis that neurofilament light (NfL) in CSF is a biomarker of CNS involvement in patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS), we measured NfL in CSF from 52 patients with lupus and 54 with pSS and explored associations with clinical, structural, immunological and biochemical abnormalities. METHODS: In CSF, we measured NfL, anti-P antibodies, protein S100B and TWEAK by ELISA and anti-NR2 antibodies by electrochemiluminescence. Anti-phospholipid antibodies and routine immunological tests were performed in blood. IgG and albumin were measured in CSF and serum for assessment of the blood-brain barrier function (Q-albumin) and intrathecal IgG production (IgG index). Cerebral MRI and neuropsychological testing were performed. RESULTS: A multivariable regression model showed that increasing CSF anti-NR2 antibody levels were associated with increasing NfL levels in patients with SLE (B 1.27, 95% CI 0.88-1.65, p < 0.001). Age contributed significantly in the model (B 0.04, 95% CI 0.03-0.05, p < 0.001). Similar findings were observed in the pSS group. Adjusted for age and sex, no associations were found between NfL levels and any MRI data. In SLE patients, higher NfL concentrations were associated with impairments in psychomotor speed and motor function, and in pSS with motor dysfunction. These associations remained in multivariable regression models. CONCLUSIONS: Increased concentration of NfL in CSF is a marker of cerebral involvement in patients with SLE and pSS, is strongly associated with the presence of anti-NR2 antibodies, and correlates with cognitive impairment in several domains.

Application and evaluation of ultrasonography in early stage of sjogren' s syndrome mice / 中国药理学通报

Aim To evaluate the application of submandibular gland ultrasound in diagnosing mouse model of Sjogren' s syndrome (SS). Methods SS model was established in C57BL/6 female mice. Hie saliva volume, water intake and body weight of mice were measured on d 0, d 21, d 28 and d 35 after the first immunization respectively, then the index and pathology of submandibular gland were detected on d 35. Meanwhile, ultrasonic examination was performed on the submandibular gland on a Vevo 2100 small animal ultrasound imaging system. The correlations between the ultrasound observations and the clinic manifestations or submandibular gland histology of SS mouse were analyzed. Results The saliva secretion of SS mice began to decrease significantly on d 28 after modeling, the index of submandibular gland increased significantly on d 35, and the typical pathological changes of SS were observ ed in submandibular gland from model mice. On d 21, it was found that a marked area increment of submandibular gland in axial section of SS mouse compared with that of normal mice. More blood flow signals were detected in submandibular gland of SS mice on d 28 and d 35. Hie analysis showed an evident correlation between the results of ultrasonic observation and the conventional detection indexes. Conclusions Ultrasonography of submandibular gland is able to provide early clues and sensitive semi-quantitative indexes for e-valuating the pathological changes of SS mouse model. It is of great value in dynamically observing the process of SS and thus it is a promising approach for pharmacodynamic studies of anti-SS drugs.

Sjogren' s syndrome with pulmonary bullae in both lungs as lung imaging performance: A case report and literature review / 吉林大学学报(医学版)

Objective: To explore the clinical characteristics of Sjogren' s syndrome (SS) with pulmonary bullae in both lungs as lung imaging performance, to analyze the common lung imaging performance of SS, and to impove the clinicians' understanding of the common lung imaging performace of the SS patients. Methods: The clinical materials, the results of bronchoscope and pathological examination of a SS patient with pulmonary bullae in both lungs as lung imaging performance were collected, and the relative literatures were reviewed. Results: A young female patient with dyspnea and hemoptysis as the chief complaint was permitted to the hospital. The physical examination results showed rampant tooth and there were no other obvious positive signs. The chest CT results showed the pulmonary bullae in both lungs. Further rheumatism examinations, corneal staining, labial gland biopsy and other assistant examinations were performed, and the patient received the related treatment. The serum immunological results indicated anti-SSA, anti-SSB, and corneal staining (+), and the rheumatoid factors were all positive; the pathology of the lower labial gland biopsy showed the number of lymphocytes in each lesion 50; the patient was diagnosed as SS finally. The patient was treated with glucocorticoids and cyclophosphamide. After the treatment, the symptoms of the patient were improved. After discharged from the hospital, the patient was treated with glucocorticoids and cyclophosphamide continuously for 2 months. However, reviewing of chest CT showed no significant changes in the lung bullae in both lungs. Conclusion: SS is a connective tissue disease with diverse clinical manifestations. When the lungs are involved, the lung imaging performance also presents no specificity. When the patient' s chest CT indicates the presence of multiple pulmonary bullae in both lungs, and no causes are find out, the possibility of SS should be considered; so that early detection and early treatment should be performed, and misdiagnosis and delay treatment of illness can be avoided.

Prevalence of inflammatory back pain and radiologic sacroiliitis is increased in patients with primary Sjögren's syndrome.

INTRODUCTION: The prevalence of Sjögren's syndrome (SS) in patients with the diagnosis of SpA has been reported to be higher than normal population. Yet, the vice-versa is unclear. In this study, we aimed to investigate the prevalence of IBP, radiologic sacroiliitis and SpA in patients with primary SS. METHODS: 85 patients followed at the rheumatology clinics of the Marmara and Kocaeli Universities with the diagnosis of primary SS between November 2011 and August 2012 were included in this study. The control group consisted of 100 age-and gender-matched patients. Inflammatory back pain and axial SpA were diagnosed according to the assessment of spondylo arthritis International Society (ASAS) criteria. RESULTS: 83 patients were (97%) female and 2 (3%) were male. Mean age of the patients was 49.1 (±11) years. Mean disease duration was 7.3 (±4) years. The patient and control groups were comparable in terms of age and gender (p > 0.05). Inflammatory back pain was observed in 21 (24.7%) of 85 primary SS patients and in 4 (4%) of 100 control subjects (p < 0.001), radiographic sacroiliitis was demonstrated in 9 (10.5%) of primary SS patients and 2 (2%) of the control subjects (p = 0.025). Remaining SpA findings were not encountered in either group. CONCLUSION: inflammatory back pain and radiologic sacroiliitis is increased in patients with primary SS. Whether IBP, SI joint inflammation and radiologic sacroiliitis is due to the co-existence of SpA and primary SS or IBP is an underdiagnosed clinical feature of SS deserves further studies of large patient numbers.

Unique Phenotypes and Functions of Follicular Helper T Cells and Regulatory T Cells in Sjögren's Syndrome.

Sjogren's syndrome (SS) is a T cell-mediated autoimmune disease of the systemic exocrine glands, such as salivary and lacrimal glands. A variety of T-cell subpopulations maintain immune tolerance in the thymus and periphery through complex immune responses including cellular and humoral immunity. The T-cell subpopulations exhibiting abnormal or unique phenotypes and impaired functionality have been reported to play important roles in the cellular mechanisms of autoimmunity in SS patients and animal models of SS. In this review, we focused on follicular helper T cells related to antibody production and regulatory T cells to control immune tolerance in the pathogenesis of SS. The unique roles of these T-cell subpopulations in the process of the onset or development of SS have been demonstrated in this review of recent publications. The clinical application of these T-cell subpopulations will be helpful for the development of new techniques for diagnosis or treatment of SS in the future.

Características salivales y estado sistémico de sujetos con xerostomía / Salivary characteristics and systemic status of subjects with xerostomia

RESUMEN: Xerostomía o sensación de boca es una afección que afecta severamente la calidad de vida de quienes la padecen. Si bien se relaciona con la reducción del flujo salival (hiposalivación), existe evidencia contradictoria y se sugiere evaluar características cualitativas salivales y estado sistémico de los afectados para comprender su etiología y mejorar terapias asociadas. El objetivo de este estudio fue comparar pH y concentración de proteínas en saliva y estado sistémico entre sujetos xerostómicos con y sin hiposialia. Se midió pH, concentración de proteínas salivales y se consignaron antecedentes sistémicos y uso de fármacos en 27 individuos xerostómicos, que fueron divididos en hiposiálicos y no hiposiálicos. Se compararon las variables mencionadas usando test no paramétrico de Mann-Whitney y test Chi-Cuadrado. Se aceptaron diferencias estadísticamente significativas con error alfa igual o menor a 5 %. Sujetos xerostómicos con hiposialia presentaron mayor prevalencia de Artritis Reumatoide y Síndrome de Sjögren en comparación con xerostómicos sin hiposialia. No se encontraron diferencias estadísticamente significativas en relación a pH, concentración de proteínas y uso de medicamentos, variables que no influirían en el padecimiento de xerostomía, independiente de la existencia de hiposialia. Sujetos con xerostomía e hiposialia presentan mayor frecuencia de Artritis Reumatoide y Síndrome de Sjögren.

ABSTRACT: Xerostomia or mouth feeling is a condition that severely affects the quality of life of thosewho suffer from it. Although it is related to the reduction of salivary flow (hyposalivation),there is contradictory evidence and it is suggested to evaluate qualitative salivarycharacteristics and systemic state of those affected in order to understand its etiology and improve associated terapies. The objective of this study was to compare saliva, pH and protein concentration and systemic status among xerostomic subjects with and without hyposialia. Were measured PH and protein concentration and were recorded systemic antecedents and drug use in 27 xerostomic individuals, who were divided into hyposalic and nonhyposalic individuals. The mentioned variables were compared using non-parametric Mann-Whitney test and Chi-Square test. Statistically significant differences were accepted with alpha error equal to or less than 0.05%. Xerostomic subjects with hyposialia presented higher prevalence of Rheumatoid Arthritis and Sjögren's Syndrome compared to xerostomics without hyposialia. No statistically significant differences were found in relation to pH, protein concentration and drug use, variables that would not influence xerostomia, independent of hyposialia. Subjects with xerostomia with hyposialia present a higher frequency of Rheumatoid Arthritis and Sjögren's Syndrome.

Salivary stimulation by prolonged release of pilocarpine in sjõgren’ syndrome

Introduction: Prolonged drug delivery in the oral cavity offers many advantages, such as reducing adverse effects. Pilocarpine is an FDA-approved parasympathomimetic drug for the treatment of glandular hypofunction; however, its adverse effects limit its use. Objective: To evaluate the stimulation of salivary flow by the use of pilocarpine-releasing films, as well as their effects on the symptoms of xerostomia and adverse effects in patients with Sjõgren’s syndrome (SS). Materials and methods: Hydroxypropylmethylcellulose (Methocel K4MCR) films were prepared in 1 percent acetic acid and pilocarpine was added under magnetic stirring. The pH and thickness, as well as diffusion uniformity and kinetics of drug release per cm2 were evaluated by spectrophotometry. The films were tested sublingually in 40 patients with Sjõgren’s syndrome for a period of two weeks. Changes in their salivary flow were evaluated by analyzing samples of total saliva. Additionally, patients were screened for symptoms of xerostomia and adverse effects. Results: The films had a pH of 2.91 +/- 0.035, a thickness of 0.06866 +/- 0.00152μm, and a diffusion uniformity of 91 percent per cm2. Use of the films resulted in an increase in salivary flow in both primary and secondary Sjõgren’s syndrome, but this increase was only significant in primary SS. Conclusion: Films showed optimal physicochemical properties for their administration, and proved effective in stimulating salivary flow without causing adverse effects during their administration.

Posible asociación autoinmune entre síndrome de Laugier-Hunziker y síndrome de Sjögren: reporte de un caso y revisión de la literatura / Laugier-Hunziker syndrome in a patient with Sjögren’s syndrome: report of one case

Laugier-Hunziker syndrome is a rare benign idiopathic condition characterized by acquired macular pigmentation of lips and buccal mucosa, often accompanied with melanonychia. The main concern with this condition is to rule out other differential diagnosis with systemic repercussions and similar hyperpigmentation patterns, such as Peutz-Jeghers syndrome, adrenal insufficiency and melanoma. We report a 58-year-old female with a 20-year history of Sjögren’s syndrome, presenting with melanonychia and hyperpigmentation in the buccal mucosa. She had no relevant medication history and is a non-smoker. The patient denied any other symptoms. The histopathology confirmed the diagnosis of Laugier-Hunziker syndrome.

Dental perspective on Sjõgren’s syndrome: literature review / Perspectiva odontológica del síndrome de Sjõgren: revisión de literatura

The human body releases around 500-600mL of saliva daily, however when values of unstimulated whole saliva range from 0.1 to 0.2mL/ min, there is a condition called Hyposalivation or hyposialia. Hyposalia is characterized by a large number of systemic conditions, including Sjõgren’s syndrome, a chronic autoimmune disease that affects between 0.1 and 3 percent of the world population and is characterized by exocrinopathy of the salivary glands leading to glandular hypofunction and thus decreasing the normal salivary flow. Saliva is part of innate immunity, when there is a decrease in protein secretion, numerous oral manifestations occur such as dental caries, candidiasis, gingival disease, angular cheilitis, lymphomas of the salivary glands, dysphagia, erythematous and fissured tongue, among others. Currently there is no defined dental treatment, however there are alternative treatments by sialogogues and salivary substitutes, plus non-pharmacological therapies, which seek to maintain the ecology and oral conditions stable, in addition to preventive and restorative dental treatment for lesions already established as a consequence of the disease. The aim of this study is to conduct a literature review on the characteristics, classification, oral manifestations and dental management of Sjõgren’s syndrome...

El ser humano secreta alrededor de 500 a 600 mL de saliva diariamente, sin embargo, al encontrarse valoresde 0.1 - 0.2 mL/min de saliva en reposo se presenta una condición llamada hiposalivación o hiposialia, la cual puedeser manifestada por una numerosa cantidad de condiciones sistémicas, entre ellas el síndrome de Sjõgren, la cual es una enfermedad autoinmune crónica presente en entre el 0.1 y3% de la población mundial, y es caracterizada por exocrinopatíade las glándulas salivales conllevando a la hipofunción glandular y disminuyendo así el flujo salival normal.Debido a que la saliva forma parte de la inmunidad innata, al presentarse una disminución en su secreción proteica sedesencadenan numerosas manifestaciones orales, tales comocaries dental, candidiasis, enfermedad gingival, queilitis angular, linfomas de las glándulas salivales, disfagia, lenguaeritematosa y fisurada, entre otras. Actualmente no existe un tratamiento odontológico definido, sin embargo se tienen alternativas de tratamiento mediante fármacos sialogogos ysustitutos salivales, además de terapias no farmacológicas, las cuales intentan mantener la ecología y las condiciones orales estables, además de los tratamientos odontológicos preventivosy restaurativos para lesiones ya establecidas por consecuenciade la enfermedad. El objetivo del presente estudio es realizar una revisión de literatura sobre las características, criterios de clasificación, manifestaciones orales y el manejoodontológico del Síndrome de Sjõgren...

Evaluación ecográfica de la glándula salival desde la perspectiva de reumatología / Evaluation of salivary gland by ultrasound from the perspective of rheumatology

The major salivary glands have multiple functions as wet oral mucosa, facilitate swallowing of food, digestion of carbohydrates, control the bacterial flora of the mouth, promote tooth mineralization and immune function by secretory IgA, which they can be altered by some conditions like autoimmune diseases or tumor. Ultrasound is a useful tool for the study of these glands, with the advantage of being safe, inexpensive, reproducible, noninvasive technique. In this review, we make a description of the anatomy and ultrasound anatomy of the major salivary glands and a brief description of the usefulness of elastography in some pathologies of these glands...

Las glándulas salivales mayores tienen múltiples funciones, como humedecer la mucosa oral, facilitar la deglución de alimentos, digestión de carbohidratos, control sobre la flora bacteriana de la boca, favorecen la mineralización de los dientes así como la función inmunológica por la secreción de IgA, las cuales pueden verse alteradas por la afección de enfermedades autoinmunes o tumorales. La ecografía es una técnica útil para el estudio de estas glándulas, con la ventaja de ser inocua, de bajo costo, reproducible y no invasiva. En esta revisión se hacen una descripción de la anatomía y sonoanatomía de las glándulas salivales mayores y una breve descripción de la utilidad de la elastografía en algunas patologías de estas glándulas...

Sjögren syndrome and neuromyelitis optica spectrum disorder co-exist in a common autoimmune milieu / Síndrome de Sjögren e espectro da neuromielite óptica coexistem em meio de autoimunidade

The relationship between Sjögren’s syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.

A relação entre síndrome de Sjögren (SS) e espectro da neuromielite óptica (ENMO) ainda não é bem compreendida. Relatamos dois pacientes com ambas as condições e revisamos 47 casos que preenchem critérios diagnósticos das duas doenças, descritos em 17 artigos extraídos da PubMed. Dos 44 pacientes cujo gênero foi informado 42 eram mulheres. A idade média ao início das manifestações neurológicas foi 36,2 anos (10-74). O anticorpo anti-AQP4 foi positivo em 32 dos 37 pacientes, em 1 foi “borderline”. Nosso Caso 1 era soronegativo para AQP4-IgG, não tinha autoanticorpos não-órgão específicos, exceto anti-SSB. O Caso 2 era soropositivo para anticorpos anti-AQP4, anti-SSA/SSB, anti-tireoglobulina, e anti-receptor da acetilcolina; apresentava hipotireoidismo, mas não havia evidêncas de miastenia gravis. Nossos casos e outros similares, previamente relatados na literatura, com resposta autoimune heterogênea à aquaporina-4 sugerem que a SS e o ENMO coexistem em meio de autoimunidade não dependente da aquaporina-4.