There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at ...a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% median 15%, interquartile range (IQR) 5–30%. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1–2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.
ObjectiveThe clinical spectrum of primary antibody deficiencies (PADs) and especially common variable immunodeficiency (CVID) includes various autoimmune disorders. We studied the prevalence and the ...features of articular rheumatic disease in a cohort of patient with PADs.MethodsIn this retrospective cohort study, complete clinical data of 268 patients with PADs, mainly consisting of patients with CVID, visiting the immunology outpatient clinic of a German tertiary hospital between 2018 and 2021 were collected. Those included case history, physical examination, laboratory as well as radiological findings.ResultsInflammatory arthritis was diagnosed in 16.4% of studied patients and was significantly more common among patients with PAD-associated enteropathy (OR 13.39, p=0.0001), splenomegaly (OR 6.09, p=0.0001) or atopic diseases (OR 3.31, p=0.021). Given HLA-B27 status, the involvement of the axial skeleton and the presence of features, such as anterior uveitis, inflammatory bowel disease, psoriasis and/or dactylitis, 75% of studied patients fulfilled the Assessment of Spondyloarthritis International Society classification criteria.ConclusionPAD-associated arthritis frequently shares features with spondyloarthritis (SpA) and enteropathic arthritis. The latter may suggest the interconnected pathomechanisms of inflammatory arthritis in SpA and PADs.
Interstitial lung disease (ILD) represents a frequent extra-glandular manifestation of primary Sjögren's Syndrome (pSS). Limited published data regarding phenotyping and treatment exists. Advances in ...managing specific ILD phenotypes have not been comprehensively explored in patients with coexisting pSS. This retrospective study aimed to phenotype lung diseases occurring in a well-described pSS-ILD cohort and describe treatment course and outcomes. Between April 2018 and February 2020, all pSS patients attending our Outpatient clinic were screened for possible lung involvement. Clinical, laboratory and high-resolution computed tomography (HRCT) findings were analyzed. Patients were classified according to HRCT findings into five groups: usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), combined pulmonary fibrosis and emphysema (CPFE), and non-specific-ILD. Lung involvement was confirmed in 31/268 pSS patients (13%). One-third (10/31) of pSS-ILD patients were Ro/SSA antibody negative. ILD at pSS diagnosis was present in 19/31 (61%) patients. The commonest phenotype was UIP
n
= 13 (43%), followed by NSIP
n
= 9 (29%), DIP
n
= 2 (6 %), CPFE
n
= 2 (6 %), and non-specific-ILD
n
= 5 (16%). Forced vital capacity (FVC) and carbon monoxide diffusion capacity (D
LCO
) appeared lower in UIP and DIP, without reaching a significant difference. Treatment focused universally on intensified immunosuppression, with 13/31 patients (42%) receiving cyclophosphamide. No anti-fibrotic treatments were used. Median follow-up was 38.2 12.4–119.6 months. Lung involvement in pSS is heterogeneous. Better phenotyping and tailored treatment may improve outcomes and requires further evaluation in larger prospective studies.
Sicca syndrome represents a heterogeneous group of conditions, such as Sjögren syndrome, causing xerophthalmiaand xerostomia. This study characterizes in depth patients with Sicca syndrome and ...evaluates salivary gland ultrasound (SGUS).
Principal component analysis and hierarchical clustering of clinical parameters, such as ESSPRI, ESSDAI and laboratory data, were performed on all referrals for assessment of Sicca symptoms between October 2018 and March 2021. SGUS and labial gland biopsies were compared across groups.
A total of 583 patients were assessed. Objective dryness was confirmed in 73% of the patients. Cluster analysis identified 3 groups with
analysis confirming distinct phenotypes:
(283/583; 49%) with more frequent symptoms but limited objective dryness;
(DAF
, 206/584; 35%), and
(DAF
, 94/584;16%). DAF
patients had highest autoantibody titers (anti-SSA(Ro) 240 vs. 3.6 vs. 3.8;
< 0.001), most extra-glandular manifestations (
< 0.001), and highest median SGUS Score (DAF
: 8 IQR 4-10 vs. SG: 2 1-4 vs. DAF
4 2-5;
< 0.001). No tangible correlation with primary Sjögren syndrome criteria was observed.
SGUS score correlated with a subset of patients with Sjögren syndrome, identified in the DAF
cluster. This study highlights heterogeneity within sicca and, indeed, Sjögren syndrome, highlighting the need for further studies.
Primary Sjögren's syndrome (pSS) is associated with an increased prevalence of traditional risk factors and cardiovascular diseases (CVDs). The study aimed to identify specific risk factors for CVD ...in pSS patients.
PSS patients with and without CVD were compared. All patients fulfilled the EULAR/ACR classification criteria. Patients with CVD presented at least one of the following manifestations: myocardial infarction, transient ischemic attacks, ischemic or hemorrhagic stroke, peripheral artery disease, coronary artery disease, and carotid plaques. Data were collected by a standardized protocol and review of medical records.
61/312 (19.6%) pSS patients presented with CVD. Traditional risk factors such as hypertension, hypercholesterinemia and diabetes (
< 0.05), pSS manifestations, in particular vasculitis (
= 0.033) and Raynaud's phenomenon (
= 0.018) were associated with CVD. Among patients with ischemic events (28/312, 9%), particularly cerebrovascular disease (
= 12/28, 42.9%), correlations with increased EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) (
= 0.039) and EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) (
= 0.048) were observed. Age at first cerebrovascular event was 55.2 48.9-69.6 years. Multivariate analysis confirmed hypertension odds ratio (OR) 3.7, 95% confidence interval (CI) 1.87-7.18,
< 0.001, hypercholesterinemia (OR 3.1, 95% CI 1.63-5.72,
< 0.001), male gender (OR 0.4, 95% CI 0.17-0.78,
= 0.009), Raynaud's phenomenon (OR 2.5, 95% CI 1.28-4.82,
= 0.007), and CNS involvement (OR 2.7, 95% CI 1.00-7.15,
= 0.048) as independent CVD predictors.
Raynaud's phenomen as well as vasculitis and high ESSDAI have shown a significant association to CVD. PSS patients with cerebrovascular events were younger than expected. Knowledge about risk factors may help clinicians to identify pSS patients at risk for CVD. After diagnosis of pSS, patients should be screened for risk factors such as hypertension and receive appropriate therapy to prevent or at least reduce sequelae such as infarction. However, further investigations are necessary in order to achieve a reliable risk stratification for these patients.
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.
ObjectivesCardiovascular comorbidities are common in patients with autoimmune diseases. This study investigates the extent of subclinical atherosclerosis in patients with primary Sjögren’s syndrome ...(pSS). Correlations with clinical factors such as organ involvement (OI) or disease activity were analysed and oxLDL antibodies (oxLDL ab) were measured as potential biomarkers of vascular damage.MethodsPatients with pSS were consecutively included from the rheumatology outpatient clinic. Age- and sex-matched controls were recruited (2:1 ratio). Data collection was performed by a standardised questionnaire and Doppler ultrasound to evaluate the plaque extent and carotid intima-media thickness (cIMT). Propensity score matching included all cardiovascular risk (CVR) factors and corresponding laboratory markers.ResultsData were available for 299 participants (199 pSS/100 controls), aged 59.4 years (50.6–65.0), 19.1% male. After matching, the pSS cohort had greater cIMT (p<0.001) and plaque extent (OR=1.82; 95% CI 1.14 to 2.95). Subgroup analyses of patients with pSS revealed that OI was associated with increased cIMT (p=0.025) and increased plaque occurrence compared with patients without OI (OR=1.74; 95% CI 1.02 to 3.01). OxLDL ab tended to be lower in patients with plaque (p=0.052). Correlations of higher Oxidized Low Density Lipoprotein (oxLDL) ab with EULAR Sjögren’s Syndrome Disease Activity Index (p<0.001) and anti–Sjögren's-syndrome-related antigen A autoantibodies (SSA/Ro antibodies) (p=0.026) were observed.ConclusionsSubclinical atherosclerosis occurs earlier and more severely in patients with pSS. The difference in cIMT between pSS and controls seems mainly driven by patients with OI, suggesting that this subgroup is particularly at risk. OxLDL ab might protect against atherosclerotic progression in patients with pSS. CVR stratification and preventive medications such as Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors should be discussed and further longitudinal studies are needed.
The phenotype of primary immunodeficiency disorders (PID), and especially common variable immunodeficiency (CVID), may be dominated by symptoms of autoimmune disorders. Furthermore, autoimmunity may ...be the first manifestation of PID, frequently preceding infections and the diagnosis of hypogammaglobulinemia, which occurs later on. In this case, distinguishing PID from hypogammaglobulinemia secondary to anti-inflammatory treatment of autoimmunity may become challenging. The aim of this study was to evaluate the diagnostic accuracy of peripheral blood lymphocyte phenotyping in resolving the diagnostic dilemma between primary and secondary hypogammaglobulinemia. Comparison of B and T cell subsets from patients with PID and patients with rheumatic disease, who developed hypogammaglobulinemia as a consequence of anti-inflammatory regimes, revealed significant differences in proportion of naïve B cells, class-switched memory B cells and CD21
B cells among B cells as well as in CD4
memory T cells and CD4
T follicular cells among CD4
T cells. Identified differences in B cell and T cell subsets, and especially in the proportion of class-switched memory B cells and CD4
T follicular cells, display a considerable diagnostic efficacy in distinguishing PID from secondary hypogammaglobulinemia due to anti-inflammatory regimens for rheumatic disease.
Background
Serology testing is explored for epidemiological research and to inform individuals after suspected infection. During the coronavirus disease 2019 (COVID-19) pandemic, frontline healthcare ...professionals (HCP) may be at particular risk for infection. No longitudinal data on functional seroconversion in HCP in regions with low COVID-19 prevalence and low pre-test probability exist.
Methods
In a large German university hospital, we performed weekly questionnaire assessments and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements with various commercial tests, a novel surrogate virus neutralisation test, and a neutralisation assay using live SARS-CoV-2.
Results
From baseline to week 6, 1080 screening measurements for anti-SARS CoV-2 (S1) IgG from 217 frontline HCP (65% female) were performed. Overall, 75.6% of HCP reported at least one symptom of respiratory infection. Self-perceived infection probability declined over time (from mean 20.1% at baseline to 12.4% in week 6,
p
< 0.001). In sera of convalescent patients with PCR-confirmed COVID-19, we measured high anti-SARS-CoV-2 IgG levels, obtained highly concordant results from enzyme-linked immunosorbent assays (ELISA) using e.g. the spike 1 (S1) protein domain and the nucleocapsid protein (NCP) as targets, and confirmed antiviral neutralisation. However, in HCP the cumulative incidence for anti-SARS-CoV-2 (S1) IgG was 1.86% for positive and 0.93% for equivocal positive results over the study period of 6 weeks. Except for one HCP, none of the eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralisation against live SARS-CoV-2. The only true seroconversion occurred without symptoms and mounted strong functional humoral immunity. Thus, the confirmed cumulative incidence for neutralizing anti-SARS-CoV-2 IgG was 0.47%.
Conclusion
When assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, we suggest confirming positive results from single measurements by alternative serology tests or functional assays. Our data highlight the need for a methodical serology screening approach in regions with low SARS-CoV-2 infection rates.
Trial Registration
The study is registered at DRKS00021152.
Objective
Extraglandular neurological manifestations of Sjögren’s syndrome are increasingly recognized, defining the disease entity of Neuro‐Sjögren. Neuropsychological assessment of patients with ...Sjögren’s syndrome has hitherto been performed on predominantly rheumatological cohorts. These studies revealed a wide variety of prevalence rates for cognitive impairment (22–80%), while variable cut‐off criteria for detection of cognitive impairment were applied. Attentional functions have not yet been thoroughly investigated in these patients, although they clearly represent relevant aspects of cognitive functioning in daily life.
Methods
We therefore conducted extensive neuropsychological assessment based on two neuropsychological test batteries i.e., the extended German version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD‐PLUS), and the test battery for attentional performance (TAP) as a well‐established assessment of attentional functions in the German‐speaking part of Europe.
Results
Sixty‐four patients with Neuro‐Sjögren, who were treated at our university hospital between December 2016 and January 2019, were included. Evidence for the presence of cognitive impairment was found in 55% of patients with Neuro‐Sjögren. The degree of cognitive impairment ranged from mild (38%) to severe (17%). Attentional and mnemonic subtests showed pronounced cognitive impairment in patients with Neuro‐Sjögren.
Interpretation
Our results suggest that a substantial proportion of patients with Neuro‐Sjögren suffer from cognitive impairment, putatively as a corollary of attentional deficits, which might exert adverse effects on occupational abilities, other cognitive functions, and social role functioning.
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