Magnetic resonance imaging (MRI) and computed tomography (CT) angiography have now largely replaced interventional angiography in the diagnoses and follow up of Takayasu arteritis (TAK) but data on ...the effects of this change of imaging method on diagnostic delay and vascular damage, and detailed data on the effect of different treatment regimens on the accumulation of vascular damage are missing. The aim of this study was to assess time trends in diagnostic delay, therapeutic approaches, arterial lesion accrual, persistent disease activity and remission rates in TAK.
The study cohort included all 78 patients from the 1999 - 2012 population-based South-East Norway TAK cohort and 19 patients from a tertiary referral cohort. TAK was classified by the 1990 American College of Rheumatology criteria and/or the 1995 modified Ishikawa diagnostic criteria. Data were retrieved by review of electronic patient journals and imaging data analyses.
Diagnostic delay fell significantly during the study period and the number of lesions at diagnoses fell from three to two. Patients diagnosed from 2000 onwards more often received up-front treatment with disease-modifying antirheumatic drugs (DMARDs) than those diagnosed before 2000 (51% vs 4%; p < 0.01), and they were more often treated with TNF inhibitors during the disease course (44% vs 14%). During the first 2 years after initiation of therapy, 10% (3/32) of TNF-inhibitor-treated patients developed new lesions, compared to 40% (16/40) on DMARD treatment (OR 0.13) and 92% (14/15) on prednisolone monotherapy (OR 0.02). Patients on TNF inhibitors had a higher sustained remission rate than patients on DMARDs (42% vs 20%; p = 0.03). From 2000 onwards, the proportion of patients without new arterial lesions during the first 5 years after diagnosis increased from 29% in the patients diagnosed in 2000-2004, to 39% in 2005-2009 and 59% of patients diagnosed in 2010-2012.
Our observational data indicate that more aggressive use of TNF inhibitors and DMARDs improve the outcome in TAK, but damage accrual is a continuous challenge and sustained remission is still relatively rare.
Objective
To study the epidemiology and clinical characteristics of Takayasu arteritis (TAK) in southeast Norway (population 2.8 million).
Methods
All study area hospital databases were screened to ...capture every potential TAK case between 1999 and 2012. These cases were manually chart reviewed, and only patients fulfilling either the 1990 American College of Rheumatology classification or the 1995 Ishikawa diagnostic criteria were included.
Results
Inclusion criteria were met by 78 patients (68 female, 10 male). Point prevalence (by 2012) segregated by ethnic origin was 22.0 per 106 (95% confidence interval 95% CI 17–29) in northern Europeans compared to 78.1 (95% CI 38–152) in Asian whites and 108.3 (95% CI 46–254) in Africans (P < 0.001). The incidence rate increased from 1 to 2 per 106 in the first to last 5‐year period of the study (P = 0.03). Northern Europeans were mean age 32.3 years at onset, and 47% had involvement confined to aortic arch branches (angiographic type I), while 24% had extensive type V disease. Mean onset age in Asian and African cases was 20.3 years and 47% had type V disease. Coexisting inflammatory bowel disease was observed in 8% and ankylosing spondylitis in 7%.
Conclusion
We report 2–4 times higher population prevalence than previously observed, and the highest prevalence ever found in Norwegians of Asian and African descent. The results support the idea that TAK in northern Europeans is marked by limited arterial involvement and older age at onset.
Exploring the associations between disease activity and medications with offspring birth weight, pre-eclampsia and preterm birth in systemic lupus erythematosus (SLE).
Data from the Medical Birth ...Registry of Norway (MBRN) were linked with data from RevNatus, a nationwide observational register recruiting women with inflammatory rheumatic diseases. Singleton births in women with SLE included in RevNatus 2006-2015 were cases (n=180). All other singleton births registered in MBRN during this time (n=498 849) served as population controls. Z-score for birth weight adjusted for gestational age and gender was calculated. Disease activity was assessed using Lupus Activity Index in Pregnancy. We compared z-scores for birth weight, pre-eclampsia and preterm birth in cases with inactive disease, cases with active disease and population controls.
Z-scores for birth weight in offspring were lower in inactive (-0.64) and active (-0.53) diseases than population controls (-0.11). Inactive disease did not predict pre-eclampsia while active disease yielded OR 5.33 and OR 3.38 compared with population controls and inactive disease, respectively. Preterm birth occurred more often in inactive (OR 2.57) and active (OR 8.66) diseases compared with population controls, and in active compared with inactive disease (OR 3.36).
SLE has an increased odds for low birth weight and preterm birth, amplified by active disease. The odds for pre-eclampsia is elevated in active, but not inactive disease. This calls for tight follow-up targeting inactive disease before and throughout pregnancy.
Objective
To assess pregnancy outcomes in an unselected Takayasu arteritis (TAK) cohort, and identify pregnancy‐related concerns.
Methods
Consenting female patients with TAK were predominantly ...recruited from a population‐based southeast Norway TAK cohort. Additional cases (n = 8) were recruited at Oslo University Hospital. Data on the number of pregnancies, births, and pregnancy outcomes before and after disease onset were retrieved from medical charts, patient questionnaires, and the Medical Birth Registry of Norway (MBRN). Data on pregnancy‐related concerns were gathered from patient questionnaires.
Results
Altogether, the 58 women in the TAK study cohort had been through 110 pregnancies, 73 (in 33 patients) before disease onset and 37 (in 23 patients) after onset. The frequencies of miscarriages, induced abortions, and maternal complications did not differ between pregnancies occurring before and after TAK onset. Pregnancy‐related hypertension was seen in 4.2% of the patients, compared to 1.5% (P = 0.37) in the reference cohort from MBRN, and preeclampsia/eclampsia in 4.5% compared to 3% (P = 0.2). The mean gestational age at delivery in pregnancies after TAK onset was 37.5 weeks, compared to 39.5 weeks in the MBRN references (P < 0.001). Cesarean sections were more frequent in deliveries after TAK onset (42%) than in MRBN controls (11%) (P < 0.001). Pregnancy‐related concerns were recorded in 80% of the TAK cohort, with 60% expressing concerns about passing the disease to offspring.
Conclusion
In this population‐based TAK cohort, the maternal and fetal outcomes were favorable. This study reveals a high prevalence of pregnancy‐related concerns in TAK patients.
To assess the effects of Rituximab (RTX) on skin and lung fibrosis in patients with systemic sclerosis (SSc) belonging to the European Scleroderma Trial and Research (EUSTAR) cohort and using a ...nested case-control design.
Inclusion criteria were fulfilment of American College of Rheumatology classification criteria for SSc, treatment with RTX and availability of follow-up data. RTX-treated patients were matched with control patients from the EUSTAR database not treated with RTX. Matching parameters for skin/lung fibrosis were the modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), follow-up duration, scleroderma subtype, disease duration and immunosuppressive co-treatment. The primary analysis was mRSS change from baseline to follow-up in the RTX group compared with the control group. Secondary analyses included change of FVC and safety measures.
63 patients treated with RTX were included in the analysis. The case-control analysis in patients with severe diffuse SSc showed that mRSS changes were larger in the RTX group versus matched controls (N=25; -24.0±5.2% vs -7.7±4.3%; p=0.03). Moreover, in RTX-treated patients, the mean mRSS was significantly reduced at follow-up compared with baseline (26.6±1.4 vs 20.3±1.8; p=0.0001). In addition, in patients with interstitial lung disease, RTX prevented significantly the further decline of FVC compared with matched controls (N=9; 0.4±4.4% vs -7.7±3.6%; p=0.02). Safety measures showed a good profile consistent with previous studies in autoimmune rheumatic diseases.
The comparison of RTX treated versus untreated matched-control SSc patients from the EUSTAR cohort demonstrated improvement of skin fibrosis and prevention of worsening lung fibrosis, supporting the therapeutic concept of B cell inhibition in SSc.
There is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sjögren's syndrome (pSS) patients. Incorporation of additional diagnostics involving ...screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients.
Liquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis.
Upregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-α signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive immune response in saliva, of cellular component assembly for saliva EVs, and of metabolism and protein folding in tears in pSS patients.
LC-MS of saliva and tears from pSS patients, solely and in combination with size-exclusion chromatography allowed screening for possible novel biomarkers encompassing both salivary and lacrimal disease target organs. This approach could provide additional diagnostic accuracy in pSS, and could possibly also be applied for staging and monitoring the disease.
AbstractBackground. In chronic inflammatory bowel disease (IBD) (Crohn's disease CD and ulcerative colitis UC), symptoms from outside the gastrointestinal tract are frequently seen, and the joints, ...skin, eyes, and hepatobiliary area are the most usually affected sites (called extraintestinal manifestations EIM). The reported prevalence varies, explained by difference in study design and populations under investigation. The aim of our study was to determine the prevalence of EIM in a population-based inception cohort in Europe and Israel. Methods. IBD patients were incepted into a cohort that was prospectively followed from 1991 to 2004. A total of 1145 patients were followed for 10 years. Results. The cumulative prevalence of first EIM was 16.9% (193/1145 patients) over a median follow-up time of 10.1 years. Patients with CD were more likely than UC patients to have immune-mediated (arthritis, eye, skin, and liver) manifestations: 20.1% versus 10.4% (p < 0.001). Most frequently seen was arthritis which was significantly more common in CD (12.9%) than in UC (8.1%), p = 0.01. Pan-colitis compared to proctitis in UC increased the risk of EIM. Conclusion. In a European inception cohort, EIMs in IBD were consistent with that seen in comparable studies. Patients with CD are twice as likely as UC patients to experience EIM, and more extensive distribution of inflammation in UC increases the risk of EIM.
Objectives: Peripheral arthritis and related musculoskeletal manifestations, often classified as peripheral spondyloarthritis, are frequently seen in patients with inflammatory bowel disease (IBD). ...Few long-term studies have reported on the prevalence of these conditions. The aim of this study was to determine the prevalence of IBD-related peripheral arthritis and peripheral spondyloarthritis in IBD patients during 20 years of disease course, and to assess whether these conditions were associated with the intestinal IBD severity and activity.
Materials and methods: In an inception cohort (the IBSEN study), IBD patients were followed prospectively for 20 years. At the 5 year follow-up the patients underwent a rheumatological examination and at the 20 year follow-up they completed a questionnaire with identical questions. When peripheral arthritis was characteristic and not explained by other specific diagnoses, it was defined as IBD-related peripheral arthritis. The Assessment of Spondyloarthritis International Society criteria were used to define peripheral spondyloarthritis, including patients with peripheral arthritis, enthesitis and/or dactylitis.
Results: After 20 years of follow-up, 441 patients were included (296 ulcerative colitis and 145 Crohn's disease). The prevalence of IBD-related peripheral arthritis was 17.2% and peripheral spondyloarthritis 27.9% during the disease course. IBD severity and activity were not different between those with a history of IBD-related peripheral arthritis or peripheral spondyloarthritis and those without. A higher proportion of women had IBD-related peripheral arthritis and peripheral spondyloarthritis.
Conclusion: During 20 years of disease course, more than every sixth patient had suffered from IBD-related peripheral arthritis and every fourth from peripheral spondyloarthritis.
Senses of smell and taste, saliva flow, and dental status are considered as important factors for the maintenance of a good nutritional status. Salivary secretory rates, chemosensory function, ...burning mouth sensation, halitosis and dental status were investigated in 58 primary Sjögren's syndrome (pSS) patients, 22 non-Sjögren's syndrome sicca (non-SS) patients, and 57 age-matched healthy controls. A significantly greater proportion of pSS and non-SS patients had ageusia, dysgeusia, burning mouth sensation, and halitosis compared to controls. Patients with pSS had significantly lower olfactory and gustatory scores, and significantly higher caries experience compared to controls. Patients with pSS and non-SS patients had significantly lower unstimulated and stimulated whole saliva secretory rates compared to controls. The findings indicated that several different aspects of oral health were compromised in both pSS and non-SS patients, and this may affect their food intake and, hence, their nutritional status. Although non-SS patients do not fulfill Sjögren's syndrome classification criteria, they have similar or, in some cases, even worse oral complaints than the pSS patients. Further studies are needed to investigate food preferences, dietary intake, and nutritional status in these two patient groups in relation to their health condition.
Chemosensory function, burning sensations in the tongue (BST), halitosis, saliva secretion, and oral health‐related quality of life (OHRQoL) were investigated in patients with primary Sjögren's ...syndrome (pSS). In 31 patients with pSS and 33 controls, olfactory and gustatory functions were evaluated. Self‐reported complaints of dysgeusia, BST, and halitosis were recorded. Saliva secretion rates were measured and OHRQoL was assessed using the short‐form Oral Health Impact Profile (OHIP‐14). Patients had significantly lower olfactory (8.8 ± 3.5 vs. 10.7 ± 1.2) and gustatory (18.9 ± 7.1 vs. 25.4 ± 4.3) scores than controls, and significantly more patients complained of dysgeusia (58.1% vs. 0%), BST (54.8% vs. 6.1%), and halitosis (41.9% vs. 0%). A significantly greater proportion of patients with pSS had ageusia (19% vs. 0%), hypogeusia (32% vs. 12%), anosmia (13% vs. 0%), or hyposmia (29% vs. 9%). Significantly lower saliva secretion rates (ml min−1) were observed in patients with pSS for stimulated (0.62 ± 0.40 vs. 1.57 ± 0.71) and unstimulated (0.08 ± 0.07 vs. 0.29 ± 0.17) saliva. The mean OHIP‐14 score was significantly higher in patients with pSS (16.2 ± 10.8 vs. 2.7 ± 3.1) and was positively correlated with dysgeusia, BST, and halitosis. In conclusion, patients with pSS reported higher occurrence of dysgeusia, BST, and halitosis, and demonstrated relatively impaired chemosensory and salivary functions. The patients’ poorer OHRQoL was associated with dysgeusia, BST, and halitosis.
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