Prevalence, correlates, and impact of sleep disturbance in Chinese patients with primary Sjögren's syndrome.

AIM: Sleep disturbances are common in primary Sjögren's syndrome (pSS) patients and may lead to disease aggravation and decreased health-related quality of life (HRQoL). There are currently no known reported studies related to the prevalence, correlates, and impact of sleep disturbance in pSS patients from China. Therefore, this study aims to assess the sleep quality in Chinese pSS patients and evaluate its relationship with the disease activity, quality of life and mood disorders. METHODS: A self-report survey was administered to 221 pSS patients and 198 healthy individuals using the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Disease activity and damage were evaluated with the European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI). Independent samples t tests, Chi-square analysis, logistic regression were used to analyze these data. RESULTS: Our results found that the prevalence of poor sleep (PSQI ≥ 6) was 57.5% and the mean global score of PSQI was 6.57 (SD 3.19) in patients, which were significantly higher than the controls (32.3% and 4.93 [SD 2.86], respectively). When trying to fall asleep, patients with pSS had some sleep disturbances, reduced sleep efficiency, increased number of awakenings than controls. There were significant correlations among dryness, ocular surface disease, HRQoL, pain, disease activity, anxiety/depression and sleep quality in pSS patients. Meanwhile, logistic regression models identified depression and Short Form-36 mental composite score as predictors of poor sleep quality. CONCLUSIONS: Sleep disturbances are commonly reported in pSS patients and sleep quality is lower in pSS patients than in healthy controls. The data suggested the need for holistic assessment and management of pSS patients.

Distal renal tubular acidosis and severe hypokalemia: a case report and review of the literature.

BACKGROUND: Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities. CASE PRESENTATION: We describe a case of a 57-year-old Caucasian woman with previous episodes of hypokalemia, severe muscle weakness, and fatigue. Upon further questioning, symptoms of dry eye and dry mouth became evident. Initial evaluation revealed hyperchloremic metabolic acidosis, severe hypokalemia, persistent alkaline urine, and a positive urinary anion gap, suggestive of distal renal tubular acidosis. Additional laboratory workup and renal biopsy led to the diagnosis of primary Sjögren's syndrome with associated acute tubulointerstitial nephritis. After potassium and bicarbonate supplementation, immunomodulatory therapy with hydroxychloroquine, azathioprine, and prednisone was started. Nonetheless, her renal function failed to improve and remained steady with an estimated glomerular filtration rate of 42 ml/min/1.73 m2. The literature on this topic was reviewed. CONCLUSIONS: Cases of renal tubular acidosis should be carefully evaluated to prevent adverse complications, uncover a potentially treatable condition, and prevent the progression to chronic kidney disease. Repeated episodes of unexplained hypokalemia could be an important clue for diagnosis.

The efficacy and safety of total glucosides of peony in the treatment of primary Sjögren's syndrome: a multi-center, randomized, double-blinded, placebo-controlled clinical trial.

To evaluate the efficacy and safety of total glucosides of peony (TGP) in adults with primary Sjögren's syndrome (pSS). A multi-center, randomized, double-blinded, placebo-controlled study was conducted between March 2012 and July 2014 at ten Chinese hospitals. In total, 320 pSS patients-classified according to the 2002 American-European Consensus Group Criteria-were randomized (2:1 ratio) to receive TGP(600 mg, tid) in the TGP group or placebo for 24 weeks in the placebo group. Study personnel, investigators, and patients were blinded to the treatment grouping. The primary endpoint was the improvement of EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) at week 24. The secondary endpoints were dry eyes/mouth/skin/nose/throat/vagina visual analogue scale (VAS), pain and discomfort VAS, fatigue VAS, mental discomfort VAS, patient global assessment (PGA), EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, basal/stimulated salivary flow-rate values, and erythrocyte sedimentation rate (ESR). All adverse events were recorded during the trial period. ESSPRI improved more in the TGP than the placebo group (p < 0.001). Dry eyes/throat/vagina VAS, fatigue VAS, mental discomfort VAS, PGA, Schirmer's test, and ESR also improved more in the TGP group than in the placebo group (all p < 0.05). Stimulated salivary flow-rate values increased in the TGP group at week 12 but not at week 24. Adverse events in TGP group were 10.9%. TGP can alleviate some dryness symptoms as well as disease activity in pSS patients over 24 weeks. TGP was well tolerated by study subjects. TGP seems to be an effective and safe treatment for pSS.

Efficacy of Pycnogenol® supplementation in remission phases of Sjögren syndrome.

BACKGROUND: The aim of this study was to evaluate the effects of Pycnogenol® supplementation in otherwise healthy subjects with Sjögren syndrome (SS) in a remission phase, who experienced persisting symptoms impairing their quality of life. METHODS: The control group receiving only standard treatment was composed of 14 subjects, the supplement group included 16 subjects who used Pycnogenol® supplementation. RESULTS: ESR and oxidative stress levels were high in all subjects at inclusion; both decreased significantly with supplementation (P<0.05). Pycnogenol® significantly improved the majority of symptoms (dry eyes and mouth dryness), diminishing the need for corticosteroids and other treatments. CONCLUSIONS: Pycnogenol® supplementation in patients with SS in a remission phase may be effective to control inflammation and reduce symptoms.

Outcomes of Thermal Pulsation Treatment for Dry Eye Syndrome in Patients With Sjogren Disease.

PURPOSE: To evaluate the clinical outcomes of thermal pulsation treatment in patients with meibomian gland dysfunction (MGD) and dry eye secondary to Sjogren disease. METHODS: Twenty-four eyes from 13 patients with previously diagnosed Sjogren disease who presented to our institution with dry eye symptoms and had thermal pulsation treatment were prospectively followed up. Patients underwent comprehensive slit-lamp examination, including MGD grading, gland oil flow, corneal and conjunctival staining scores, and tear break-up time (TBUT). Tear osmolarity was tested before and after treatment. RESULTS: The average patient age was 62.4 years (range, 31-78 yrs); 12 were women and 1 a man. The average meibomian gland oil flow score showed an increase from pretreatment 0.71 to 1.75 at 1 year posttreatment (range 9-15 months) (P = 0.001). The average corneal staining score decreased from a pretreatment grade of 1.04 to a posttreatment grade of 0.36 (P < 0.001). The average conjunctival staining score decreased from a pretreatment grade of 1.5 to a posttreatment grade of 0.48 (P < 0.001). The average tear break-up time improved from 3.8 seconds before treatment to 7.5 seconds after thermal pulsation treatment (P < 0.001). There was no statistically significant change in the tear osmolarity or Ocular Surface Disease Index score. CONCLUSIONS: Our findings suggest that MGD is an important contributor to dry eye disease in patients with Sjogren disease and should not be overlooked when considering treatment options. Thermal pulsation is a therapeutic option for patients with Sjogren disease who have MGD and dry eye symptoms. After a single treatment, patients exhibited increased oil flow and tear break-up time with an associated decrease in corneal and conjunctival staining.

Sjogren's syndrome from the perspective of ophthalmology.

Sjogren's syndrome (SS) is an autoimmune disease affecting the lacrimal glands resulting in dry eye disease (DED). Ophthalmologists may be the first line of detection of Sjogren's syndrome given the frequency of DED in SS and that dry eye is often the presenting symptom. Numerous symptom questionnaires and tests have been developed to help diagnose DED, but as of yet, there is no "gold standard." Minimally invasive objective metrics are needed for a reliable diagnosis of DED. Currently there is no single test to diagnose SS-associated DED. Although there are several approaches to treatment, none are specific for DED in SS, and, generally, several methods need to be tried to find what works best for a specific patient. Treatment for DED continues to be an unmet medical need, especially given that DED in SS is typically on the severe end of the spectrum.

Endogenous event-related potentials in patients with primary Sjögren's syndrome without central nervous system involvement.

OBJECTIVES: Endogenous cognitive event-related potentials (CERPs) reflect higher-level processing of sensory information and can be used to evaluate cognitive functions. The aim of this paper was to determine whether there are any abnormalities in the electrophysiological parameters of CERPs in patients with primary Sjögren's syndrome (pSS) but without symptoms of central nervous system (CNS) involvement or mental disorder. The analysis of CERP parameters was then correlated with the clinical status of the patients and with some of the immunological parameters in the patient group. METHOD: Thirty consecutive patients with pSS (29 females, one male) were included in the study. All the patients underwent CERP examination. RESULTS: There was a significant prolongation of the latency of P300 and N200 potentials in patients with pSS. Abnormalities in electrophysiological parameters of CERPs correlated with the duration of the disease, salivary gland abnormalities, and elevated erythrocyte sedimentation rate (ESR) values. Patients with coexisting chronic fatigue syndrome (CFS) had larger P300 amplitudes. There were no statistically significant changes in the electrophysiological parameters of CERPs in patients with pSS dependent on the presence of peripheral nervous system (PNS) lesions, skin changes, arthritis, abnormalities in white blood cells and the immune system or the levels of blood lipids. CONCLUSIONS: The results of the study suggest the presence of a minor cognitive dysfunction in patients with pSS without symptoms of CNS involvement or mental disorder. Cognitive dysfunction correlated with the disease duration time and the severity of inflammatory changes (salivary gland abnormalities and inflammatory markers in the blood). Further and larger longitudinal studies are necessary for confirmation of this correlation.

Effect of laser acupuncture on salivary flow rate in patients with Sjögren's syndrome.

Sjögren's syndrome (SS) is a multisystem autoimmune disease characterized by hypofunction of the salivary and lacrimal glands, frequently relieved with symptomatic treatments, such as saliva substitutes, eye lubricants, and cholinergic stimulators. The aim of this pilot randomized placebo-controlled study was to estimate the effects of laser acupuncture on salivary flow rates in patients with severe hyposalivation due to SS. A prospective cohort of 26 female patients affected by SS has been evaluated. The laser therapy equipment used was the Pointer Pulse, emitting light in the red visible spectrum (650 nm), with a power of 5 mW and an irradiation time of 120 s per acupoint, in an area of 3.14 mm(2) (fluence = 19.2 J/cm(2), power density = 0.16 W/cm(2), total dose = 0.6 J). The following acupuncture points were stimulated bilaterally: LI 2 Erjian, ST 5 Daying, ST 6 Jiache, ST 7 Xiaguan, SI 19 Tinggong, and BL 13 Feishu. True laser acupuncture led to a significantly higher amount of saliva production, measured after the end of the protocol (5 weeks), and during the 6-month follow-up period. The results are stable from the end of the protocol until the 3rd month of follow-up; during the last control, a slight but significant decrease in production has also been shown. This preliminary study proposes laser acupuncture as a possible treatment for improving salivary flow rates in patients with SS, but further validation on a larger sample is still necessary.

[Mechanism of cardiac function changes in rat models of Sjogren's syndrome based on Keap1-Nrf2/ARE signaling pathways].

OBJECTIVE: To investigate the mechanism underlying the changes in the cardiac function in rat models of Sjogren's syndrome (SS) based on Kelch-like ECH-associated protein 1 (Keap1)-Nrf2/ARE signaling pathways. METHODS: Thirty male Wistar rats were randomly divided into two groups, normal control (NC) group and SS model group, with 15 in each. The rats in the model group were injected with the complete Freund's adjuvant plus homologous antigen of submandibular gland (0.2 mL mixture) into bilateral posterior paw metatarsus. The body mass, water intake, submandibular gland index, spleen index, and histological changes of the glands were observed 30 days after inflammation was induced. Cardiac function was assessed using invasive hemodynamic monitoring. Meanwhile, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC), IL-18, IL-35 were detected using ELISA; ROS and reactive nitrogen species (RNS), glutathione (GSH), thioredoxin (TrX) protein were determined using immunohistochemical staining. The expressions of Keap 1, nuclear factor erythroid 2-related factor (Nrf2), macrophage activating factor (Maf) antioxidant responsive element (ARE) mRNAs were detected using real-time fluorescent quantitative PCR (qRT-PCR); the levels of heme oxygenase-1 (HO-1), γ-glutamic acid and a half long glycine synthetase (γ-GCS) proteins in cardiac tissue were examined using Western blotting. RESULTS: Compared with the NC group, the model group presented reduced body mass, submandibular gland index and spleen index (P<0.05), increased water intake (P<0.01), heart rate (HR), heart index (HI), left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVEDP) (P<0.05), and decreased left ventricular ±dp/dtmax (P<0.05). Compared with the NC group, the model group had increased IL-18, MDA, RNS, TAC, ROS levels, and Keap1, Maf, Nfr2 mRNAs, HO-1, γ-GCS protein expressions in the heart tissue, while TrX, GSH, IL-5 and SOD levels decreased significantly (P<0.01). CONCLUSION: The immune imbalance in SS rats may be related with the up-regulated levels of Keap1, Maf, Nfr2 mRNAs, HO-1, γ-GCS.

Visante optical coherence tomography and tear function test evaluation of cholinergic treatment response in patients with sjögren syndrome.

PURPOSE: To evaluate tear meniscus changes in patients with Sjögren syndrome (SS) receiving oral pilocarpine with Visante optical coherence tomography (OCT). METHODS: Eight patients with primary SS were recruited in this prospective interventional case series study. Patients received pilocarpine tablets twice a day for 3 months. Visual analog scale assessment for dry eye and dry mouth symptoms was carried out. Patients underwent OCT and slit-lamp microscopy graticule scale tear meniscus height (TMH) measurements, strip meniscometry testing, tear film breakup time measurement, fluorescein and Rose Bengal staining, and the Schirmer 1 test. The data were analyzed 1 week, 1 month, and 3 months after treatment. Mann-Whitney test was performed. RESULTS: Visual analog scale assessment showed a significant time-wise improvement (P < 0.05). OCT and graticule scale TMH measurements significantly improved after 1 week (P < 0.05), 1 month, and 3 months of treatment (P < 0.001). Strip meniscometry, mean tear film stability, and fluorescein and Rose Bengal scores remained improved 3 months after treatment (P < 0.001), whereas Schirmer 1 test values tended to improve without statistical significance. CONCLUSIONS: Visante OCT was effective in monitoring tear meniscus changes during the course of treatment noninvasively and quickly. Oral pilocarpine seemed to be effective in improving TMH, and the signs and symptoms of dryness in patients with SS.

Tratamiento de fondo del síndrome seco. ¿Qué puede aportar el reumatólogo? / Etiologic treatment of sicca syndrome. What can the rheumatologist offer?

En el síndrome de Sjögren primario (SSP) no se ha descrito hasta el momento una terapia eficaz para las manifestaciones glandulares a pesar del desarrollo de múltiples agentes orales y biológicos en los últimos años. Varios fármacos empleados como tratamiento de fondo en otras enfermedades se han probado empíricamente y, reconocida la hiperactividad de la célula B en el SSP, también los moduladores de estas se han ensayado en esta enfermedad. En este artículo se revisan los datos existentes sobre el uso de tratamientos modificadores de la enfermedad exclusivamente en el síndrome seco, encontrando que los ensayos publicados con fármacos antirreumáticos orales han mostrado resultados contradictorios y desalentadores, mientras que algunos tratamientos biológicos han resultado esperanzadores. Los problemas encontrados se centran sobre todo en la falta de una correcta y homogénea metodología en los diseños de los ensayos (AU)

No effective treatment has been documented for the glandular primary Sjögren syndrome (PSS) despite the development of oral and biologic agents that have significant activity against other autoimmune disorders. Some disease-modifying agents have been empirically evaluated for the treatment of PSS. Targeting B cells also seems very promising in SSP because of the B-cell hyperactivity recognized in this desease. This article reviews existing data on the use of disease-modifying therapy for glandular of SSP. To date, published studies and trials of oral DMARDs for the treatment of SSP have shown disappointing results. B-cell modulation is clearly a promising therapy for PSS. Many challenges in trial design and execution are evident from the studies reviewed (AU)

Effect of neuromuscular electrical stimulation in a patient with Sjogren's syndrome with dysphagia: a real time videofluoroscopic swallowing study.

Severe dysphagia in a 54 year-old woman with Sjogren's syndrome with involvement of multiple cranial nerves significantly improved after treatment with neuromuscular electrical stimulation (NMES) in combination with a swallowing rehabilitation program. The swallowing response was assessed in real time using a videofluoroscope. Immediate improvement in the tongue retraction force, clearing of the valleculae, increase in laryngeal elevation and shortening of pharyngeal transit time were noted during stimulation. The patient returned to independent oral feeding after 46 sessions of NMES. After follow-up for 1 year, we found that the patient maintained adequate oral feeding and did not show signs of pulmonary complications.

A new approach to managing oral manifestations of Sjogren's syndrome and skin manifestations of lupus.

Sjogren's syndrome (SS) is an autoimmune disorder that affects the salivary glands, leading to xerostomia, and the lacrimal glands, resulting in xerophthalmia. Secondary SS is associated with other autoimmune disorders such as systemic rheumatic diseases and systemic lupus erythematosis (SLE), which can affect multiple organs, including the epidermis. Recent studies have demonstrated that green tea polyphenols (GTPs) possess both anti-inflammatory and anti-apoptotic properties in normal human cells. Epidemiological evidence has indicated that, in comparison to the United States, the incidence of SS, clinical xerostomia and lupus is considerably lower in China and Japan, the two leading green tea-consuming countries.Thus, GTPs might be responsible, in part, for geographical differences in the incidence of xerostomia by reducing the initiation or severity of SS and lupus. Consistent with this, molecular, cellular and animal studies indicate that GTPs could provide protective effects against autoimmune reactions in salivary glands and skin. Therefore, salivary tissues and epidermal keratinocytes could be primary targets for novel therapies using GTPs. This review article evaluates the currently available research data on GTPs, focusing on their potential application in the treatment of the oral manifestations of SS and skin manifestations of SLE.

Comparison of autologous serum eye drops with conventional therapy in a randomised controlled crossover trial for ocular surface disease.

AIMS: To evaluate the efficacy of 50% autologous serum drops against conventional treatment in ocular surface disorders refractory to normal treatments in a prospective randomised crossover trial. METHOD: Patients fulfilling ophthalmological and haematological entry criteria were randomised to either 3 months of autologous serum 50% followed by 3 months of their conventional treatment, or 3 months of conventional treatment, followed by 3 months of autologous serum. Clinical assessments, including Schirmer's test, rose Bengal, and fluorescein staining, were carried out on entry and at monthly intervals. Impression cytology was performed at entry, 3 and 6 months. Grading was carried out on degrees of squamous metaplasia and goblet cell density. Subjective comfort was recorded daily using the "faces" scale. These categorical scores were converted to linear measurement using Rasch analysis. Statistical analysis was carried out using Wilcoxon's signed rank test and ANOVA. RESULTS: 16 patients were recruited with 31 eyes studied. The ocular surface diseases chiefly included Sjögren's syndrome (n = 6) and keratoconjunctivitis sicca (n = 5). Impression cytology available in 25 of 31 eyes showed significant improvement on serum treatment, p<0.02. Rasch weighted faces scores were statistically significantly better with serum, p<0.01. CONCLUSION: The results of this randomised study provide further evidence of the beneficial effects of autologous serum in severe ocular surface disorders. For most of these patients, autologous serum was superior to conventional treatment for improving ocular surface health and subjective comfort.

Objective auscultation for traditional chinese medical diagnosis using novel acoustic parameters.

The goal of this work is to propose novel acoustic parameters of voice for the purpose of providing a quantitative analysis of auscultation in traditional Chinese medical diagnosis. There is rare amount of available literature related to this topic. Four novel acoustic parameters, the average number of zero-crossings, the variations in local peaks and valleys, the variations in first and second formant frequencies, and the spectral energy ratio, are presented to analyze and identify the characteristics among non-vacuity, qi-vacuity, and yin-vacuity subjects. Among these acoustic parameters, two temporal parameters, the average number of zero-crossings and the variations in local peaks and valleys, outperformed other parameters in classifying both non-vacuity and deficient subjects. The spectral energy ratio was adequate for the classification between qi-vacuity and yin-vacuity patients. This research is a first step in an ongoing effort to modernize the auscultation in traditional Chinese medical diagnosis.

Sjögren's syndrome: a model for dental care in the 21st century.

The diagnosis and treatment of Sjögren's syndrome, which poses many severe complications, should be of critical interest to dentists, who are often the first practitioners to detect symptoms. Dentistry is an integral part of health care delivery for patients with this condition. Management of Sjögren's syndrome can be seen as a model for the expanded scope of dental care in the future.

Sindrome de Sjogren, posibilidades de tratamiento homeopatico / Sjogren Syndrome, homeopathic treatment possibilities

Presentamos una revision de las actualidades fisiopatologicas y terapeuticas del sindrome de Sjogren(SS), enfermedad autoinmune que se considera la segunda en prevalencia en los Estados Unidos, solo por detras de la Artritis Reumatoidea(AR). Asimismo incluimos un planteamiento teorico acerca de los medicamentos homeopaticos que pudiesen ser utiles en la terapia de esta enfermedad con base en el conocimiento de sus componentes y los mecanismos patologicos que estos producen, ademas de los resultados observados en un grupo de 6 pacientes con SS y manejados con homeopatia por un periodo de 3 a 6 meses posteriores al tratamiento. El resultado ha sido una remision total de los sintomas durante el tiempo que se tomo el medicamento, y en algunos casos, 6 meses despues de suspenderse este.

Sindrome de Sjogren, posibilidades de tratamiento homeopatico / Sjogren Syndrome, homeopathic treatment possibilities

Presentamos una revision de las actualidades fisiopatologicas y terapeuticas del sindrome de Sjogren(SS), enfermedad autoinmune que se considera la segunda en prevalencia en los Estados Unidos, solo por detras de la Artritis Reumatoidea(AR). Asimismo incluimos un planteamiento teorico acerca de los medicamentos homeopaticos que pudiesen ser utiles en la terapia de esta enfermedad con base en el conocimiento de sus componentes y los mecanismos patologicos que estos producen, ademas de los resultados observados en un grupo de 6 pacientes con SS y manejados con homeopatia por un periodo de 3 a 6 meses posteriores al tratamiento. El resultado ha sido una remision total de los sintomas durante el tiempo que se tomo el medicamento, y en algunos casos, 6 meses despues de suspenderse este.(AU)

Effects on local blood flux of acupuncture stimulation used to treat xerostomia in patients suffering from Sjögren's syndrome.

Twenty-one patients with Sjögren's syndrome were given four different kinds of acupuncture stimulation, at acupuncture points previously used to treat xerostomia. The local blood flux in the skin overlying the parotid gland was measured with laser Doppler flowmetry before, during and after the acupuncture stimulation. The results showed that the local blood flux increased significantly during and after both manual acupuncture and low-frequency (2 Hz) electro-acupuncture as compared with superficial acupuncture. These results indicate that acupuncture induced an increase in the local blood flux which was more pronounced for those patients who had previously reacted with increased salivary flow to acupuncture.