Sjögren's syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a wide spectrum of sensory modalities and distribution patterns. The objective of this ...cross-sectional study was to determine characteristics of Sjögren's syndrome as a cause for severe neuropathy with limb weakness.
One hundred and eighty four patients with polyneuropathy associated with limb weakness underwent routine diagnostics including investigations for Sjögren's syndrome. Forty-four patients with Sjögren's syndrome (ACR-EULAR classification criteria) and severe neuropathy were identified.
Sjögren's syndrome was found at a median age of 63 years and the gender distribution showed a balanced female-male ratio of 1:1. Anti-SSA(Ro) antibodies were detected in 48% while seronegative patients were diagnosed with Sjögren's syndrome based on sialadenitis on minor salivary gland biopsy with a focus score ≥1. The majority of patients (93%) were diagnosed with Sjögren's syndrome after neurological symptoms appeared. Limbs were symmetrically involved in 84% of patients (57% tetraparesis, 27% paraparesis). Sensory function was not affected in 11% of patients indicating that Sjögren's syndrome associated neuropathy can present as a pure motor syndrome. Electrophysiological measurements did not reveal pathognomonic findings (23% demyelinating pattern, 36% axonal pattern, 41% both demyelinating and axonal damage signs). More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging.
Our findings show that severe neuropathy with limb weakness is often associated with Sjögren's syndrome. This is of great importance in identifying and understanding the causes of immune mediated polyneuropathy.
CIDP associated with Sjögren’s syndrome Seeliger, Tabea; Gingele, Stefan; Bönig, Lena ...
Journal of neurology,
08/2021, Letnik:
268, Številka:
8
Journal Article
Recenzirano
Background
This study addresses the challenging characterisation and differentiation of CIDP versus CIDP in association with Sjögren’s syndrome to facilitate the process in clinical routine.
Methods
...Patients with both CIDP and Sjögren’s syndrome and CIDP without Sjögren’s syndrome were compared concerning relevant differences in clinical, laboratory and electrophysiological findings. 154 patients who fulfilled the diagnostic EFNS/PNS criteria for CIDP were included in the analysis. 54 of these patients additionally fulfilled the ACR/EULAR classification criteria for Sjögren’s syndrome.
Results
The frequency of female patients was higher in patients with CIDP and Sjögren’s syndrome (52%) versus CIDP patients without Sjögren’s syndrome (28%). Furthermore, the occurrence of cranial nerve impairment was significantly higher in patients with Sjögren’s syndrome (39% versus 14%). There were no significant group differences in the evaluation of initial symptoms, severity of disability judged by INCAT disability scale score, presence or distribution of sensory deficits, limb weakness and the presence of ataxia, pain or dysautonomia, CSF laboratory or electrophysiological findings.
Conclusions
In conclusion, our data indicate that cranial nerve impairment and female gender might represent red flags for an additional Sjögren’s syndrome in patients with CIDP. The patterns of clinical disabilities and electrophysiological findings due to peripheral nerve damage are similar in both CIDP entities.
Blood-cerebrospinal fluid (CSF) barrier dysfunction is pivotal for diagnosing immune-mediated neuropathies, especially in spinal nerve root inflammation. Typically, either total CSF protein or the ...CSF to serum albumin ratio (Q
) is measured. Total CSF protein measurements have limitations, notably its fixed reference value regardless of age, in contrast to the age-dependent reference for Q
. Our goal was to evaluate both markers in patients with immune-mediated neuropathies.
In our multicenter research, we collected retrospective CSF data from patients suffering from immune-mediated neuropathies across four German research centers. These parameters were analyzed in relation to their clinical characteristics.
Out of 419 samples, 36 (8.6%) displayed a notable variation between total CSF protein and Q
values. A detailed analysis revealed that patients displaying elevated Q
but normal total CSF protein levels were significantly younger at disease onset (
= 0.01), at the time of diagnosis (
= 0.005), and when undergoing lumbar puncture (
= 0.001) compared to patients with elevated CSF protein and normal Q
levels. These effects were especially evident for the subgroup of samples derived by female patients.
Our work confirms the crucial role of Q
in diagnosing immune-mediated neuropathies and particularly its efficacy as a marker for evaluating the blood-CSF barrier in patients with an earlier disease onset. Considering the significance of the albumin quotient, its assessment is especially advisable in younger patients of female sex to avoid missing a potential barrier dysfunction that might be falsely negative when using total protein.
Background:
IgPro20 is the first approved subcutaneous immunoglobulin (SCIg) preparation for the treatment of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Two different ...doses of the SCIg preparation were investigated in the pivotal PATH study. Real-world data, and particularly the efficacy of an equivalent dose switch from intravenous immunoglobulin (IVIg) to SCIg, are still not available.
Methods:
In this prospective observational study, 41 patients with CIDP treated with intravenous immunoglobulin (IVIg) were changed to an equivalent (1:1) dose of IgPro20 1 week after last IVIg treatment. Patients were examined at the time of switch from IVIg to SCIg, after 3 and after 6 months and efficacy, treatment preferences and systemic and local reactions were assessed.
Results:
Various clinical outcome parameters demonstrated overall stability regarding disability, general activity and social participation, grip and muscle strength, as well as gait impairment. Treatment satisfaction remained unchanged between IVIg and SCIg therapy. However, 88% of patients favoured treatment with subcutaneous IgPro20 over IVIg 6 months after switch to IgPro20.
Conclusion:
Results demonstrate that the switch of IVIg to an equivalent dose of SCIg represents an effective and preferred treatment option for CIDP patients.
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.
Background
Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune‐related adverse events (irAE). ...Especially ICI‐mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing.
Methods
A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut‐off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed.
Results
nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher‐grade nAE had significantly elevated serum‐concentrations of monocyte chemoattractant protein 1 (MCP‐1) and brain‐derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05).
Conclusion
Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP‐1 and BDNF are potentially the first clinical‐class nAE predictors for patients under ICI therapy.
Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors. However, there is a growing awareness of immune‐related adverse events, especially neurological adverse events (nAE). MCP‐1 and BDNF are potentially the first clinical‐class nAE predictors for patients under immune checkpoint inhibitor therapy.
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.
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.
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.
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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