Sleep behaviour differs in women and men with psoriatic arthritis and axial spondyloarthritis with impact on quality of life and depressive symptoms.

OBJECTIVES: Axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) may have a profound impact on sleep and health-related quality of life. The aim of this study was to assess sleep quality and quality of life and determine associated factors in patients treated with spondyloarthritides (SpA). METHODS: Cross-sectional questionnaire-based assessment of sleep behaviour, quality of life, functional impairment and depression (Regensburg Insomnia Scale, WHO Quality of Life questionnaire, Funktionsfragebogen Hannover questionnaire, Beck Depression Inventory II, Patient health questionnaire 9) and retrospective medical chart analysis of a monocentric cohort of 330 patients with SpA (n=168 PsA and n=162 axSpA). RESULTS: 46.6% of patients with SpA demonstrated abnormal sleep behaviour. Linear regression models showed HLA-B27 positivity, Bath Ankylosing Spondylitis Disease Activity Index, depressive symptoms, functional capacity and disease duration to be predictive of insomnia symptoms in axSpA, respectively, depressive symptoms, female sex and Disease Activity Score 28 in patients with PsA. Patients with unrestful sleep had a significantly reduced health-related quality of life (p<0.001) as well as significantly more depressive symptoms (p<0.001). Satisfaction with health was rated significantly lower (p<0.001), indicating poor sleep as a burden on general well-being.In particular, female patients had a significantly worse sleep quality with a prolonged sleep latency (p=0.009), increased sleep disturbances (p=0.014) and unrestful sleep (p<0.001) as well as a reduced physical and mental health-related quality of life (p=0.015, p<0.001) and more depressive symptoms (p=0.015). CONCLUSION: Despite treatment, many patients with SpA demonstrate abnormal sleep behaviour with symptoms of insomnia and a reduced quality of life with significant differences between male and female patients. An interdisciplinary and holistic approach may be needed to address unmet needs.

Inflammatory stays inflammatory: a subgroup of systemic sclerosis characterized by high morbidity and inflammatory resistance to cyclophosphamide.

BACKGROUND/PURPOSE: Elevated levels of C-reactive protein (CRP) in systemic sclerosis (SSc) have been linked to early inflammatory stages of the disease. This study has been designed to investigate CRP levels longitudinally in a cohort of SSc patients and to correlate these findings with comorbidities and disease characteristics. METHODS: In this retrospective study, patients with SSc treated at the outpatient clinic of the Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, were analyzed. Only patients with at least three consecutive visits and at least 1 year follow-up were included in this study. CRP serum levels were measured at every visit and categorized as positive if CRP concentrations were ≥ 5 mg/l. Subjects with elevated CRP levels at more than 80% of visits were defined as inflammatory SSc. The longitudinal CRP profiles were correlated with disease characteristics and comorbidities. RESULTS: A total of 1815 consecutive visits of 131 SSc patients were analyzed. Over the observed time span (7.6 (1.0-19.5) years), 18.3% (n = 24) of patients had continuously elevated CRP levels (inflammatory SSc), whereas in 29% (n = 38), CRP levels were always in the normal range. There was no association between disease duration and CRP levels at first visit. Inflammatory SSc was associated with male gender (p = 0.022), anti-Scl-70 antibodies (p = 0.009), diffuse cutaneous SSc (p = 0.036), pulmonary fibrosis (p < 0.001), rheumatoid arthritis (p = 0.007), and cardiac arrhythmia (p = 0.048). Moreover, patients with inflammatory SSc revealed higher modified Rodnan skin scores (p < 0.001); lower forced vital capacity (FVC) (p < 0.001), total lung capacity (p = 0.001), and diffusing capacity (p = 0.008); and faster decline of FVC per year (p = 0.007). Even treatment with cyclophosphamide (CYC) did not decrease CRP levels (p = 0.754). CONCLUSION: Inflammatory SSc is characterized by a more severe phenotype, high morbidity, and a large proportion of male patients. Even treatment with CYC does not alter CRP levels in this subpopulation with a high unmet medical need.

Serological lymphocytic activity and patient-reported outcomes in Sjögren's syndrome.

This study was set to investigate whether serum markers of lymphocytic activity are associated with patient-reported outcomes in Sjögren's syndrome (SS). Forty-six patients with SS were included in this cross-sectional study. Patients with monoclonal gammopathy, history of malignant lymphoma, or with secondary SS were excluded. Serum levels of IgG, ß2-microglobulin (ß2M), soluble interleukin-2 receptor (sIL2-R), and free light chains (FLC) were assessed. Systemic disease activity was measured by the EULAR SS disease activity index (ESSDAI). Patient-reported symptoms were recorded by visual analogue scales (VAS) of pain, fatigue, and dryness, as compiled in the EULAR SS patient-reported index (ESSPRI). Depressive symptoms were determined by the Patient Health Questionnaire 9 (PHQ-9). Serum concentrations of κFLC (r = 0.491, p = 0.001), λFLC (r = 0.326, p = 0.027), and ß2M (r = 0.421, p = 0.004) correlated with the ESSDAI, whereas sIL-2R and IgG did not. No correlations between serum markers of lymphocytic activity and the ESSPRI, or single VAS measures of pain, dryness, or fatigue, were found. In patients with VAS fatigue scores in the upper quartile, sIL-2R serum levels were even decreased (p = 0.019). Only depressive symptoms as determined by PHQ-9 were positively correlated with fatigue (r = 0.536, p < 0.001). In this well-defined cohort of patients with SS, serological lymphocytic activity was not correlated with patient-reported outcomes and sIL-2R levels were even decreased in patients with high fatigue scores. Only depressive symptoms were correlated with fatigue. This highlights the need to further understand the link between inflammation and disease characteristics in SS.

Association of High Mobility Group Box Chromosomal Protein 1 and Receptor for Advanced Glycation End Products Serum Concentrations With Extraglandular Involvement and Disease Activity in Sjögren's Syndrome.

OBJECTIVE: To assess serum levels of high mobility group box chromosomal protein 1 (HMGB-1) and the soluble receptor for advanced glycation end products (sRAGE) in patients with Sjögren's syndrome (SS) and explore correlations with disease activity. METHODS: Thirty-nine patients with SS and 21 healthy controls were included in this cross-sectional study. Clinical and laboratory values were obtained from all patients. Disease activity was assessed using the European League Against Rheumatism SS Disease Activity Index (ESSDAI). Serum samples were collected and HMGB-1 and sRAGE levels were measured using enzyme-linked immunosorbent assay (ELISA), and HMGB-1 concentrations were semiquantified by Western blotting. RESULTS: In ELISA, HMGB-1 serum levels did not differ between healthy controls and patients with SS (P = 0.783). When measured by semiquantitative Western blotting, HMGB-1 levels were increased in patients with SS compared to healthy controls (P = 0.012). HMGB-1 serum levels detected by Western blotting were higher in patients with extraglandular manifestations (P = 0.003) and were correlated with ESSDAI disease activity (r = 0.544, P < 0.0001). Furthermore, sRAGE was elevated in the sera of patients with SS (P = 0.003) compared to healthy controls and was also correlated with the ESSDAI (r = 0.545, P = 0.002). CONCLUSION: Serum levels of total HMGB-1 and sRAGE were elevated in patients with SS compared to healthy controls and correlated with disease activity as measured by the ESSDAI. Patients with extraglandular involvement had high serum levels of HMGB-1.