In Primary Sjögren's Syndrome (PSS), there is an apparent lack of data concerning the perspectives of patients, their needs, preferences and difficulties of daily life. This qualitative study was ...conducted to explore perspectives and needs of patients with PSS that influence health related quality of life (HRQL).
We recruited 20 PSS patients fulfilling the American-European consensus classification criteria out of the PSS cohort of the Medical University Graz, Austria. In total, 6 focus group sessions (with three to four patients per group) were performed. A modified meaning condensation procedure was used to analyse the data.
The interview analysis resulted in 484 meaning units, 254 subconcepts and 86 concepts. The identified concepts were grouped into three dimensions: physical dimension, psychological & emotional challenges and social life & daily living. A dependency between the three categories was identified. The concepts most commonly reported by patients were related to the physical dimension: pain and dryness as well as complaints associated with/provoked by these symptoms. Patients also reported shortness of breath, fatigue und constipation.
This qualitative study underpins that HRQL in PSS patients is affected by several factors. The problems are not limited to dryness, pain and fatigue while the complaints secondary to these symptoms are important to patients with PSS significantly affecting physical, psychological and social life components of HRQL. A disease-specific patient related outcome measures for clinical practice and trials should be developed considering the different aspects of HRQL in PSS.
Abstract
Darier disease (DD) is a rare, inherited multi-organ disorder associated with mutations in the
ATP2A2
gene. DD patients often have skin involvement characterized by malodorous, inflamed skin ...and recurrent, severe infections. Therapeutic options are limited and inadequate for the long-term management of this chronic disease. The aim of this study was to characterize the cutaneous immune infiltrate in DD skin lesions in detail and to identify new therapeutic targets. Using gene and protein expression profiling assays including scRNA sequencing, we demonstrate enhanced expression of Th17-related genes and cytokines and increased numbers of Th17 cells in six DD patients. We provide evidence that targeting the IL-17/IL-23 axis in a case series of three DD patients with monoclonal antibodies is efficacious with significant clinical improvement. As DD is a chronic, relapsing disease, our findings might pave the way toward additional options for the long-term management of skin inflammation in patients with DD.
(1) Background: Psoriatic Arthritis (PsA) is a painful disease of the joints and spine. Recent reports observed distinct enteric dysbiosis in PsA; intake of probiotic strains is considered to ...ameliorate enteric dysbiosis. If probiotics are effective in PsA is elusive. (2) Methods: In this pilot open-label study we enrolled 10 PsA patients with low to medium disease activity who received probiotics for 12 weeks. Analysis of faecal zonulin, α1-antitrypsin and calprotectin, as well as peripheral immune phenotyping was performed at baseline, after 12 weeks and 12 weeks after termination of probiotic intake. (3) Results: All patients showed increased levels of the enteric permeability marker zonulin which correlated with the frequency of peripheral Th17 cells. Calprotectin, a marker for intestinal inflammation was elevated in 6 out of 10 patients. Probiotic intake resulted in a reduction of disease activity and gut permeability. These effects, however, were not sustained beyond termination of probiotic intake. (4) Conclusions: PsA patients suffer from enhanced enteric permeability and inflammation. Probiotics may ameliorate disease activity in PsA by targeting these alterations.
Aims:
Line immune-assays (LIA) for the detection of myositis-specific antibodies (MSA) are used widely for characterization of idiopathic inflammatory myopathies (IIM). Their current use and ...significance for the diagnosis of IIM remains unclear.
Methods:
In this retrospective analysis, we retrieved clinical diagnoses of patients tested for MSA and myositis-associated antibodies (MAA) Jo-1, Mi-2α, Mi-2β, TIF1γ, SRP, MDA-5, NXP-2, SAE, PL-7, PL-12, EJ, OJ, PM-Scl100, PM-Scl75 and Ku. We calculated clinical specificity, clinical sensitivity, negative- and positive predictive values (PPV) as well as positive and negative likelihood ratios.
Results:
In total, we analyzed 3167 samples. After exclusion of repeated measurements and patients with insufficient clinical information, data of 1118 patients were available for analysis. A total of 242 patients tested positive for at least one antibody, of which 45 patients had a diagnosis of IIM; 25 IIM patients were negative for all MSA/MAA. Clinical specificity of MSA/MAA for the diagnosis of IIM ranged between 94.2% and 99.9%. Clinical sensitivity and PPV across all antibodies tested ranged from 0.0% to 12.9% and 0.0% to 72.7%, respectively.
Conclusion:
In clinical practice MSA/MAA are used widely for diagnostic work-up of IIM, resulting in a low pre-test probability. Clinicians should be aware that PPVs for most MSA/MAA are low.
It is estimated that 50-70% of patients with rheumatoid arthritis (RA) are non-adherent to their recommended treatment. Non-adherent patients have a higher risk of not reaching an optimal clinical ...outcome. We explored factors associated with nonadherence from the patient's perspective.
Four hundred and fifty-nine RA patients (346 (75.4%) females; mean age 63.0 ± 14.8 years) who failed to attend follow-up visits in two rheumatology centres were eligible to participate in a qualitative interview study. We used this strategy to identify patients who were potentially non-adherent to medicines and/or non-pharmacological interventions. By means of meaning condensation analysis, we identified new and some already well known insights to factors associated with non-adherence. We used the capability, opportunity, and motivation model of behaviour (COM-B) model as a frame of reference to classify the factors.
Forty-three of 131 patients (32.8%) who agreed to participate in the qualitative interviews were found to be non-adherent. New insights on factors associated with non-adherence included strong opinions of patients, such as pain being considered as an indicator of hard work and something to be proud of, or inflammation being a natural process that should not be suppressed; feeling not to be in expert's hands when being treated by a physician/health professional; the experience of excessive self-control over the treatment; and rheumatologists addressing only drugs and omitting non-pharmacological aspects. The COM-B model comprehensively covered the range of our findings.
The new insights on factors associated with non-adherence allow a better understanding of this phenomenon and can substantially enhance patient care by helping to develop targeted interventions.
Background: The etiology of autoimmune rheumatic diseases is unknown. Endothelial dysfunction and premature atherosclerosis are commonly seen in these patients. Atherosclerosis is considered one of ...the main causes of cardiovascular diseases. Hypertension is considered the most important traditional cardiovascular risk. This case-control study aimed to investigate the relationship between autoimmune diseases and cardiovascular risk. Methods: This study was carried out in patients with rheumatoid arthritis, RA (n = 10), primary Sjögren syndrome, PSS (n = 10), and healthy controls (n = 10). Mean blood pressure (MBP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse wave velocity (PWV, an indicator of arterial stiffness) were assessed via a Vicorder device. Asymmetric dimethylarginine (ADMA) was measured via ELISA. Retinal photos were taken via a CR-2 retinal camera, and retinal microvasculature analysis was carried out. T-tests were conducted to compare the disease and control groups. ANOVA and ANOVA—ANCOVA were also used for the correction of covariates. Results: A high prevalence of hypertension was seen in RA (80% of cases) and PSS (40% of cases) compared to controls (only 20% of cases). Significant changes were seen in MBP (RA 101 ± 11 mmHg; PSS 93 ± 10 mm Hg vs. controls 88 ± 7 mmHg, p = 0.010), SBP (148 ± 16 mmHg in RA vs. 135 ± 16 mmHg in PSS vs. 128 ± 11 mmHg in control group; p = 0.007), DBP (77 ± 8 mmHg in RA, 72 ± 8 mmHg in PSS vs. 67 ± 6 mmHg in control; p = 0.010 in RA compared to the controls). Patients with PSS showed no significant difference as compared to controls (MBP: p = 0.240, SBP: p = 0.340, DBP: p = 0.190). Increased plasma ADMA was seen in RA (0.45 ± 0.069 ng/mL) and PSS (0.43 ± 0.060 ng/mL) patients as compared to controls (0.38 ± 0.059 ng/mL). ADMA in RA vs. control was statistically significant (p = 0.022). However, no differences were seen in ADMA in PSS vs. controls. PWV and retinal microvasculature did not differ across the three groups. Conclusions: The prevalence of hypertension in our cohort was very high. Similarly, signs of endothelial dysfunction were seen in autoimmune rheumatic diseases. As hypertension and endothelial dysfunction are important contributing risk factors for cardiovascular diseases, the association of hypertension and endothelial dysfunction should be monitored closely in autoimmune diseases.
The purpose of this study was to investigate the value of real-time sonoelastography (RTS) of salivary glands for the diagnosis and assessment of glandular damage in primary Sjögren's syndrome (pSS). ...After institutional review board approval, 45 pSS patients, 24 sicca patients and 11 healthy controls were investigated prospectively. Questionnaires were completed and Saxon and Schirmer tests and routine blood tests carried out in all patients. All patients underwent B-mode ultrasonography and RTS of parotid and submandibular glands. Abnormal findings were graded from 0 to 48 and from 0 to 16, respectively. Sialoscintigraphy was done according to a routine protocol; scoring ranged from 0 to 12. Statistical analysis comprised receiver operating characteristic curve and multivariate regression analysis. Patients with pSS had higher B-mode (median score = 25 range: 2-44 vs. 9 1-20, p < 0.001) and RTS (6.5 2-13 versus 4 1-9, p < 0.001) scores than controls with sicca syndrome, yielding areas under the curve of 0.83 and 0.85 (p < 0.05 each), respectively for pSS diagnosis. In cases with an inconclusive B-mode ultrasonography result, RTS (cutoff score: ≥ 6) led to a sensitive (66.7%) and specific (85.7%) classification of patients and sicca controls. In multivariate regression analysis, RTS (regression coefficient = -0.48, p = 0.005), but not B-mode ultrasonography, reflected impaired salivary gland function according to the Saxon test, whereas none of the subjective measures of dryness or discomfort were related to ultrasonography results. B-mode and RTS results were both associated with sialoscintigraphy scores (regression coefficient = 0.66, p < 0.001, and regression coefficient = 0.55, p = 0.001, respectively). Reproducibility of B-mode ultrasonography and RTS was good, with intra-class correlation coefficients of 0.93 (95% confidence interval: 0.57-0.98) and 0.93 (95% confidence interval: 0.79-0.98), respectively. In summary, RTS might be a useful adjunct to B-mode ultrasonography for diagnosis and assessment of salivary gland impairment in primary Sjögren's syndrome.
Chronic arthropathy occurs in approximately two thirds of patients with hereditary haemochromatosis (HH). The aim was to study inflammatory and structural lesions in patients with HH with (HH-A) and ...without arthropathy (HH-WA) using ultrasonography.
This was a cross-sectional study of 26 patients with HH-A, 24 with HH-WA and 37 with hand osteoarthritis (HOA). Clinical examination was performed in 68 joints, and we retrieved data on hand function, pain and global disease activity (all using a visual analogue scale (VAS)), morning stiffness and ferritin levels. Standard x-ray and ultrasound were conducted in 36 joints (hands, hips, knees and ankles), and we graded grey scale synovitis (GSS), power Doppler ultrasound (PD), osteophytes, erosions, tenosynovitis and cartilage damage semi-quantitatively in accordance with prior publications.
Ultrasound revealed a high proportion of inflammatory changes in HH-A; GSS was found in 96.2% and PD signals in 80.8% of patients (median GSS score 9, PD score 2.5). The frequency of these findings was similar in HOA. Inflammation was also common in HH-WA, yielding GSS in 83.3% and PD signals in 50.0% of patients. Cartilage damage was most prominent in HH-A as compared to HH-WA and HOA (median scores 11.0, 2.5 and 2.0, respectively). The prevalence and extent of erosions and osteophytes were similar in all groups. None of the ultrasound scores was associated with pain or function; GSS, PD, osteophyte and cartilage scores correlated with x-ray-verified structural damage.
A high prevalence of ultrasound-verified inflammation and cartilage damage was found in HH-A, and to a lesser extent in HH-WA. These findings were associated with x-ray-verified damage but not with clinical scores of pain and function.
A peripheral blood type I interferon (IFN) gene signature can be found in approximately 50% of patients with rheumatoid arthritis (RA),1 suggesting that activation of the type I IFN system ...contributes to RA pathogenesis within this subset of patients. Therefore, the question arises whether blocking the type I IFN response, especially in patients with a high type I IFN gene signature, would be an effective treatment approach for RA. To address this question and to estimate the potential for the future planning of a larger study, we conducted a randomised, double-blind, placebo-controlled multicentre pilot trial, in which we planned to include 24 patients with RA with active disease and a high type I IFN gene signature to receive the type I IFN receptor blocking antibody anifrolumab2 or placebo intravenously every 4 weeks for a total of six doses (trial registration number NCT03435601; start of study: December 2017; end of study: November 2020). Inclusion criteria, among others, were current treatment with a conventional synthetic disease-modifying antirheumatic drug (DMARD) and failure to clinically respond to at least one Tumor necrosis factor alpha (TNF)-inhibitor but no more than a total of three biological DMARDs; patients had to have moderately to highly active disease. To identify patients with RA with a high IFN signature, we applied a four-gene (IFI27, IFI44, IFI44L, RSAD2) quantitative PCR-based test (QIAGEN) using RNA extracted from whole blood collected in PAXgene Blood RNA tubes (PreAnalytiX).3 Recruitment turned out difficult not least because of the evolution of the COVID-19 pandemic and, therefore, the study was prematurely stopped. Here, we report on the overall results of this pilot trial.
Abstract Objectives To study the association of clinical and/or ultrasound variables with patients′ (PGA) and physicians′ (EGA) global assessment of disease activity in Psoriatic Arthritis (PsA). The ...correlation of these parameters with the discordance between PGA and EGA, as well as with PGA/EGA changes over 6 months was also investigated. Methods Prospective study of 83 consecutive PsA patients with 2 visits scheduled 6 months apart. All patients underwent the following assessments: tender (TJC) and swollen joint count (SJC), PASI, dactylitis and Leeds enthesitis index. PGA, patients′ level of pain (pain VAS), EGA, and HAQ were also recorded. Grey scale (GS) and Power Doppler (PD) ultrasound were performed at 68 joints (evaluating synovia and tendons) and 14 entheses. Regression analyses were performed to assess the association of these variables with PGA and EGA. Two new variables ‘PGAminus EGA′ and ‘PGAchange-EGAchange′ were developed to explore the discrepancy between PGA and EGA and the consistency of PGA/EGA changes over time, respectively. Results The parameters explaining most of PGA and EGA variability were pain VAS (30.5%) and SJC (48.5%), respectively. The correlation between EGA and joint counts was stronger in patients with high versus low levels of ultrasound verified inflammation. PGAminus EGA was mainly explained by pain and SJC. Pain was the most important predictor of PGA change whereas TJC and HAQ were more closely associated with EGA changes. ‘PGAchange-EGAchange′ was linked to pain and SJC. Ultrasound scores were not linked with either of these variables. Conclusions Pain VAS and joint counts are the most important clinical parameters explaining patients′ and physicians′ perception of disease activity, whereas the correlation of active inflammation as verified by sonography with these factors is limited.
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