Sleep quality in patients with primary Sjögren's syndrome

Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables.Objective To assess the sleep quality in primary Sjögren’s syndrome (pSS) patients and evaluate its relationship with the disease, quality of life and mood disorders. Methods The sleep quality of 29 pSS women and 29 matched controls was assessed by the Pittsburgh Sleep Quality Index (PSQI). Seven domains are grouped according to three factors: F1 perceived sleep quality (subjective sleep quality, sleep latency, use of sleeping medication), F2 sleep efficiency (sleep duration, habitual sleep efficiency) and F3 daily disturbances (sleep disturbances, daytime dysfunction). These domains are scored as a single factor of global sleep quality. The Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scale and Hospital Anxiety and Depression Scale (HADS) were also administered. Disease activity and damage were evaluated with the EULAR Sjögren’s syndrome disease activity index (ESSDAI), the Sjögren’s Syndrome Disease Activity and Damage Indexes (SSDAI, SSDDI). Results The mean PSQI global score had higher pathological values (8.6±4.6) compared with controls (5.6±2.2) (p=0.002). F1 and F3 were significantly worse in cases (p=0.01, p=0.009). A negative correlation was found between SF-36 subscales and the global PSQI, F2 and F3. The anxiety HADS correlated with F2 and F3, while depression only with F3. No correlation with FACIT and disease indexes emerged. Conclusion Using PSQI, an impaired sleep quality was demonstrated in pSS patients, especially with perceived quality and the daily disturbances. It is associated with a reduced quality of life but not with disease-related variables

Autologous Hematopoietic Stem Cell Transplantation for Treatment of Systemic Sclerosis

Systemic Sclerosis (SSc) is a complex autoimmune disease, characterized by high mortality and morbidity. The heterogeneity in terms of extent, severity, and rate of progression of skin and internal organ involvement gives rise to many difficulties in finding the optimal therapeutic interventions for SSc and, to date, no disease-modifying agents are available. In this scenario, it is not surprising that SSc was one of the first autoimmune diseases challenged with high-dose immunosuppressive treatment followed by autologous hematopoietic stem cell transplantation (AHSCT). In the last decades, AHSCT has emerged as a treatment option for refractory SSc through a reduction of the aberrant immune cells, followed by re-constitution of a new, self-tolerant immune system. After several case series and pilot studies, more recently three randomized controlled trials have shown a benefit in skin involvement, organ functions and quality of life measures in AHSCT compared to monthly cyclophosphamide. In addition, although AHSCT presents a certain risk of mortality, it has been shown that the overall survival is better, compared to the cyclophosphamide group. Current evidence suggests that SSc patients who are most likely to benefit from AHSCT are early, active, with rapidly progressing diffuse skin disease, and mild involvement of internal organs. As the studies have progressed, it has become evident the need for a more rigorous patient selection, the optimization of transplant and post-transplant procedures, and the intervention of multidisciplinary teams of specialists to increase the safety and efficacy of AHSCT in SSc

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

Epidemiological profile and north-south gradient driving baseline systemic involvement of primary Sjogren's syndrome

Objective: To characterize the systemic phenotype of primary Sjögren’s syndrome at diagnosis by analysing the EULAR-SS disease activity index (ESSDAI) scores. Methods: The Sjögren Big Data Consortium is an international, multicentre registry based on worldwide data-sharing cooperative merging of pre-existing databases from leading centres in clinical research in Sjögren’s syndrome from the five continents. Results: The cohort included 10 007 patients (9352 female, mean 53 years) with recorded ESSDAI scores available. At diagnosis, the mean total ESSDAI score was 6.1; 81.8% of patients had systemic activity (ESSDAI score ≥1). Males had a higher mean ESSDAI (8.1 vs 6.0, P < 0.001) compared with females, as did patients diagnosed at <35 years (6.7 vs 5.6 in patients diagnosed at >65 years, P < 0.001). The highest global ESSDAI score was reported in Black/African Americans, followed by White, Asian and Hispanic patients (6.7, 6.5, 5.4 and 4.8, respectively; P < 0.001). The frequency of involvement of each systemic organ also differed between ethnic groups, with Black/African American patients showing the highest frequencies in the lymphadenopathy, articular, peripheral nervous system, CNS and biological domains, White patients in the glandular, cutaneous and muscular domains, Asian patients in the pulmonary, renal and haematological domains and Hispanic patients in the constitutional domain. Systemic activity measured by the ESSDAI, clinical ESSDAI (clinESSDAI) and disease activity states was higher in patients from southern countries (P < 0.001). Conclusion: The systemic phenotype of primary Sjögren’s syndrome is strongly influenced by personal determinants such as age, gender, ethnicity and place of residence, which are key geoepidemiological players in driving the expression of systemic disease at diagnosis.

Capitolo 7.6 Spondiloartriti enteropatiche

Le artriti enteropatiche, il cui concetto fu per la prima volta introdotto da Moll e Wright nel 1976, sono un gruppo di artropatie associato a malattie infiammatorie croniche intestinali (inflammatory bowel diseases - IBD), in particolare la malattia di Crohn (MC) e la rettocolite ulcerosa (RCU), e ad altre forme tra cui la sindrome da by-pass intestinale e l’artropatia associata a celiachia. Sono classificate nella più ampia categoria delle spondiloartriti (SpA), con cui condividono caratteristiche cliniche, radiologiche, sierologiche e genetiche

Instruments for Outcome Evaluation of Specific Domains in Primary Sjögren’s Syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disorder characterized by very heterogeneous features. The spectrum of this disorder may vary from benign but disabling symptoms such as dryness, due to lachrymal and salivary involvement, pain and fatigue, to systemic, potentially severe, manifestations that may involve any organ. In recent decades, the arrival of biotechnological therapy has offered new opportunities for the treatment of this—until now—orphan disease. Currently, the possible use of these new drugs in therapeutic trials has made it necessary to have reliable outcome measures to evaluate their efficacy in this disease. A great effort has been made in multicenter, often multinational, studies to develop and validate instruments capable of assessing the different disease-related features. The adoption in therapeutic trials of the newly developed outcome measures aimed at assessing systemic features and patient reported symptoms has often yielded disappointing results. These negative data have been ascribed, on the one hand, to the trial design not being completely appropriate, and, on the other hand, to the fact that a single instrument may be not sufficient to cover the great clinical heterogeneity of the disease features. There is now growing belief that composite end points that include instruments that are able to assess the various aspects of the disease may be more properly and successfully used in future therapeutic trials

Interleukin 18: A Biomarker for Differential Diagnosis Between Adult-onset Still's Disease and Sepsis.

OBJECTIVE: The differential diagnosis between rheumatic diseases and infectious conditions is a great challenge in clinical practice. Adult-onset Still's disease (AOSD) is a rare systemic inflammatory syndrome that shares several clinical and laboratory variables with sepsis. Interleukin (IL)-18 is overexpressed in AOSD, suggesting a possible role as a disease biomarker. The aim of our study was to detect IL-18 serum levels in a cohort of patients with AOSD and sepsis and to address its possible role as a biomarker for differential diagnosis. METHODS: A group of unselected patients with AOSD diagnosed according to the Yamaguchi criteria and consecutive patients with sepsis diagnosed according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria were enrolled. The clinical and laboratory data were collected. In the AOSD group, disease activity was assessed by Pouchot's and Rau's criteria. IL-18 serum levels were detected by ELISA. RESULTS: Thirty-nine patients with AOSD and 18 patients with sepsis were enrolled. Two out of 18 patients with sepsis (11.1%) also fulfilled the Yamaguchi criteria. A significant difference was found in IL-18 serum levels between patients with active and inactive disease (p < 0.001), and it positively correlated with disease activity (p = 0.0003), ferritin serum level (p = 0.016), and erythrocyte sedimentation rate (p = 0.041). IL-18 was significantly increased in patients with AOSD when compared with sepsis (p = 0.014). For a cutoff of 148.9 pg/ml, this test had a specificity of 78.3% and a sensitivity of 88.6%. CONCLUSION: We have demonstrated that IL-18 can be a biomarker for differential diagnosis between AOSD and sepsis