The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe ...extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization.
Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression.
The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions.
This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is ∼15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and is extremely heterogeneous in terms of immunological features and clinical manifestations. This complexity could result in a ...delay in the diagnosis and treatment introduction, with impacts on long-term outcomes. In this view, the application of innovative tools, such as machine learning models (MLMs), could be useful. Thus, the purpose of the present review is to provide the reader with information about the possible application of artificial intelligence in SLE patients from a medical perspective. To summarize, several studies have applied MLMs in large cohorts in different disease-related fields. In particular, the majority of studies focused on diagnosis and pathogenesis, disease-related manifestations, in particular Lupus Nephritis, outcomes and treatment. Nonetheless, some studies focused on peculiar features, such as pregnancy and quality of life. The review of published data demonstrated the proposal of several models with good performance, suggesting the possible application of MLMs in the SLE scenario.
To assess the relationship between resilience and several diseases and individual features in primary Sjӧgren's Syndrome (SS) patients. Resilience was assessed using the Resilience Scale (RS-14). ...Disease activity, damage, and reported symptoms were assessed by means of ESSDAI (EULAR Sjögren's syndrome disease activity index), SSDDI (Sjӧgren's Syndrome Disease Damage Index) and ESSPRI (EULAR Sjӧgren's Syndrome Patient Reported Index). EuroQol, HADS (Hospital Anxiety and Depression Scale), SF-12 (Short-form 12 health survey), FAS (Fatigue Assessment Scale), FACIT-F (Functional Assessment of Chronic Illness Therapy – Fatigue), and IPAQ (International Physical Activity Questionnaire) questionnaires were submitted to evaluate physical and mental well-being of the recruited patients. Data about the autoimmune profile, systemic manifestations, and current therapy were collected. Educational qualifications and work activities were also considered. Descriptive, correlational, and linear regression analysis were performed. 74 consecutive women with primary SS and 74 sex and age-matched healthy subjects as a control group were recruited. SS patients displayed a moderate value of resilience (median 78.5) with no significant difference compared to controls (
p
= 0.38). An inverse relationship was found between resilience and mood disorders such as anxiety (
p
= 0.038) and depression (
p
< 0.001). Greater resilience was associated with a better perception of the quality of life (
p
= 0.02) and general health (
p
< 0.001), as well as with less fatigue (
p
= 0.008) and a more physically active lifestyle (
p
= 0.001). No significant relationship was found neither between resilience and age, socio-demographic and disease characteristics, nor with ESSDAI (
p
= 0.26), ESSPRI (
p
= 0.83) and SSDDI (
p
= 0.67). This is the first study assessing resilience in a large group of unselected primary SS patients. Most resilient primary SS patients are less depressed and show a better perception of their health. Greater resilience tends to correlate with less anxiety, physical and mental fatigue, and a more active lifestyle, while no association with disease activity and duration, damage, and socio-demographic features was detected. Considering the well-known role of resilience in helping to better cope with chronic illnesses, its assessment in SS patients should not be overlooked and the possible strategies for its improvement should be better explored and further implemented.
Objective
Salivary gland epithelial cells (SGECs) are key cellular drivers in the pathogenesis of primary Sjögren's syndrome (SS); however, the mechanisms sustaining SGEC activation in primary SS ...remain unclear. We undertook this study to determine the role of autophagy in the survival and activation of SGECs in primary SS.
Methods
Primary SGECs isolated from the minor SGs of patients with primary SS or sicca syndrome were evaluated by flow cytometry, immunoblotting, and immunofluorescence to assess autophagy (autophagic flux, light chain 3 IIB LC3‐IIB, p62, LC3‐IIB+/lysosome‐associated membrane protein 1 LAMP‐1 staining), apoptosis (annexin V/propidium iodide PI, caspase 3), and activation (intercellular adhesion molecule, vascular cell adhesion molecule). Focus score and germinal center presence were assessed in the SGs from the same patients to assess correlation with histologic severity. Human SG (HSG) cells were stimulated in vitro with peripheral blood mononuclear cells (PBMCs) and serum from primary SS patients in the presence or absence of autophagy inhibitors to determine changes in autophagy and epithelial cell activation.
Results
SGECs from primary SS patients (n = 24) exhibited increased autophagy (autophagic flux P = 0.001; LC3‐IIB P = 0.02; p62 P = 0.064; and as indicated by LC3‐IIB/LAMP‐1+ staining), increased expression of antiapoptotic molecules (Bcl‐2 P = 0.006), and reduced apoptosis (annexin V/PI P = 0.002; caspase 3 P = 0.057), compared to samples from patients with sicca syndrome (n = 16). Autophagy correlated with histologic disease severity. In vitro experiments on HSG cells stimulated with serum and PBMCs from primary SS patients confirmed activation of autophagy and expression of adhesion molecules, which was reverted upon pharmacologic inhibition of autophagy.
Conclusion
In primary SS SGECs, inflammation induces autophagy and prosurvival mechanisms, which promote SGEC activation and mirror histologic severity. These findings indicate that autophagy is a central contributor to the pathogenesis of primary SS and a new therapeutic target.
The prevalence of peripheral nervous system (PNS) involvement in primary Sjögren's syndrome (pSS) has been reported to range from 2% to over 50%. Bias in study designs, including low number of ...patients and unclearly defined rheumatological and neurological diagnosis could explain such variability. Consequently, the exact depiction of PNS involvement in pSS is still lacking. This study aimed at analyzing the prevalence and the clinical and laboratory factors associated with PNS involvement in a very large cohort of well-characterized pSS patients with a clearly defined neurological diagnosis.
Clinical and serological data of 1,695 pSS patients with specific and accurate information on PNS involvement were analyzed. Comparisons between patients with and without PNS involvement and between patients with distinct subsets of PNS manifestations were performed.
Prevalence of PNS involvement was 3.7%. The most frequent types observed were pure sensory neuropathies and axonal sensorimotor polyneuropathies (SMP). Patients with PNS involvement exhibited a more active disease profile and were more frequently treated with immunosuppressants. Intriguingly, clinical and serological negative prognostic factors, including purpura, extra-glandular manifestations, leukopenia, low complement and cryoglobulinemia, principally characterized patients with SMP, while subjects with pure sensory neuropathy displayed a milder phenotype.
Our results highlight that PNS involvement is rather rare, but prognostically relevant in pSS. Main adverse prognostic features characterize patients with SMP, while pure sensory neuropathies are usually associated with a mild clinical picture. These findings, useful for patient stratification, may suggest protean pathogenic pathways underlying different types of PNS manifestations in pSS.
Salivary gland ultrasonography (SGUS) is increasingly applied for the management of primary Sjögren's syndrome (pSS). This study aims to: (i) compare the reliability between two SGUS scores; (ii) ...test the reliability among sonographers with different levels of experience.
In the reliability exercise, two four-grade semi-quantitative SGUS scoring systems, namely De Vita et al. and OMERACT, were tested. The sonographers involved in work-package 7 of the HarmonicSS project from nine countries in Europe were invited to participate. Different levels of sonographers were identified on the basis of their SGUS experience and of the knowledge of the tested scores. A dedicated atlas was used as support for SGUS scoring.
Twenty sonographers participated in the two rounds of the reliability exercise. The intra-rater reliability for both scores was almost perfect, with a Light's kappa of 0.86 for the De Vita et al. score and 0.87 for the OMERACT score. The inter-rater reliability for the De Vita et al. and the OMERACT score was substantial with Light's Kappa of 0.75 and 0.77, respectively. Furthermore, no significant difference was noticed among sonographers with different levels of experience.
The two tested SGUS scores are reliable for the evaluation of major salivary glands in pSS, and even less-expert sonographers could be reliable if adequately instructed.
Data on the safety of anti-SARS-CoV-2 vaccines in patients with rare rheumatic diseases, such as systemic vasculitis (SV), are limited. The aim of this study was to evaluate the occurrence of a ...disease flare and the appearance of adverse events (AEs) following administration of anti-SARS-CoV-2 vaccine in a multicentre cohort of patients with SV.
Patients with SV and healthy controls (HC) from two different Italian rheumatology centres were asked to complete a questionnaire assessing disease flares occurrence, defined as new onset of clinical manifestations related to vasculitis needing an implementation of therapy, and local/systemic AEs appearance following anti SARS-CoV-2 vaccination.
107 patients with SV (57 ANCA-associated) and 107 HC were enrolled. A disease flare occurred in only one patient (0.93%) with microscopic polyangiitis after the first dose of an mRNA vaccine. After both the first and the second vaccine dose administration, no significant differences in AEs between patients with SV and HC were observed; no serious AEs were reported as well.
These data suggest a good risk profile for anti-SARS-CoV-2 vaccine in patients with systemic vasculitis.
The aim of this study was to assess the clinical and laboratory features of a cohort of Italian patients with adult-onset Still disease (AOSD) with particular attention on possible life-threatening ...complications.
The clinical charts of 41 consecutive Italian patients with AOSD referred to our rheumatological department over the last 10 years were retrospectively examined. Data regarding clinical manifestations, laboratory features and complications were collected and compared with those reported in literature.
The most frequent manifestations were: fever (90.2%), arthralgias (80.4%), skin rash (75.6%), sore throat (53.6%), arthritis (51.2%), lymphadenopathy (48.7%), hepatosplenomegaly (41.4%), myalgia (21.9%), fatigue (12%), diarrhoea and vomiting (9.7%), pleural effusion (9.7%), pericardial effusion (4.8%) and abdominal pain (2.4%). In two patients whose cases are described in detail; the course of the disease was complicated by disseminated intravascular coagulopathy, in one patient with a fatal outcome. ESR, CRP and leucocyte count mean values were 69.41 mm/h, 69.05 mg/l and 18,798.5 cell/mm(3) (neutrophils 84.64%), respectively. Serum ferritin levels were increased in 48.7% of patients while transaminases were elevated in 42.6% of patients (71% considering only patients in an active phase of disease).
The results of this study are in line with those reported for other cohorts of patients. Even if the prognosis of AOSD is considered favourable, the present study indicates that the disease is a troubling condition needing prompt intervention. Occasionally, AOSD may rapidly worsen with life-threatening events.
Immune and vascular ageing are proposed risk factors for giant cell arteritis (GCA). Data on the impact of age at diagnosis of GCA on the clinical presentation and course of the disease are scarce.
...Patients with GCA followed at referral centres within the Italian Society of Rheumatology Vasculitis Study Group were enrolled up to November 2021. Patients were grouped according to age at diagnosis: ≤64, 65-79 and ≥80 years old.
The study included 1004 patients, mean age 72.1±8.4, female 70.82%. Median follow-up duration was 49 (IQR 23-91) months. Patients in the oldest group (≥80 years) had significantly more cranial symptoms, ischaemic complications and risk for blindness compared with the groups 65-79 and ≤64 years (blindness: 36.98% vs 18.21% vs 6.19%; p<0.0001). Large-vessel-GCA was more frequent in the youngest group (65% of patients). Relapses occurred in 47% of patients. Age did not influence the time to first relapse, nor the number of relapses. Older age was negatively associated with the number of adjunctive immunosuppressants. Patients >65 years old had 2-3 fold increased risk for aortic aneurysm/dissection up to 60 months follow-up. Serious infections, but not other treatment-related complications (hypertension, diabetes, osteoporotic fractures), were significantly associated with older age. Mortality occurred in 5.8% of the population with age >65, cranial and systemic symptoms as independent risk factors.
The highest risk of ischaemic complications, aneurysm development, serious infections and the possible undertreatment make of GCA a very challenging disease in the oldest patients.
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