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1.	Alberdi-Saugstrup, Mikel, et al. (författare) High-sensitive CRP as a predictive marker of long-term outcome in juvenile idiopathic arthritis 2017 Ingår i: Rheumatology International. - : SPRINGER HEIDELBERG. - 0172-8172 .- 1437-160X. ; 37:5, s. 695-703 Tidskriftsartikel (refereegranskat)abstract To evaluate whether C-reactive protein (CRP), including variation within the normal range, is predictive of long-term disease outcome in Juvenile Idiopathic Arthritis (JIA). Consecutive patients with newly diagnosed JIA were included prospectively from defined geographic areas of the Nordic countries from 1997 to 2000. Inclusion criteria were availability of a baseline serum sample within 12 months after disease onset and 8-year clinical assessment data. Systemic onset JIA was not included. CRP was measured by high-sensitive ELISA (detection limit of 0.2 mg/l). One hundred and thirty participants with a median follow-up time of 97 months (range 95-100) were included. At follow-up, 38% of the patients were in remission off medication. Absence of remission was associated with elevated level of CRP at baseline (odds ratio (OR) 1.33, confidence interval (CI) 1.08-1.63, p = 0.007). By applying a cutoff at the normal upper limit (> 10 mg/l), the risk of not achieving remission was increased to an OR of 8.60 (CI 2.98-24.81, p < 0.001). Variations of CRP within the normal range had no predictive impact on disease activity at follow-up. Baseline levels of ESR were available in 80 patients (61%) and elevated ESR was associated with absence of remission in a multivariable logistic regression analysis (OR 2.32, CI 1.35-4.00, p = 0.002). This results of this study indicate that baseline CRP concentrations above 10 mg/l are predictive of a poor outcome at 8-year follow-up. We could not demonstrate any predictive value of CRP variations within the normal range.
2.	Alberdi-Saugstrup, M, et al. (författare) Non-HLA gene polymorphisms in juvenile idiopathic arthritis: associations with disease outcome. 2017 Ingår i: Scandinavian journal of rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; , s. 1-8 Tidskriftsartikel (refereegranskat)abstract To test the hypothesis that non-HLA single-nucleotide polymorphisms (SNPs) associated with the risk of juvenile idiopathic arthritis (JIA) are risk factors for an unfavourable disease outcome at long-term follow-up.The Nordic JIA cohort is a prospective multicentre study cohort of patients from the Nordic countries. In all, 193 patients met the inclusion criteria of having an 8year follow-up assessment and available DNA sample. Seventeen SNPs met the inclusion criteria of having significant associations with JIA in at least two previous independent study cohorts. Clinical endpoints were disease remission, actively inflamed joints and joints with limitation of motion (LOM), articular or extra-articular damage, and history of uveitis.Evidence of associations between genotypes and endpoints were found for STAT4, ADAD1-IL2-IL21, PTPN2, and VTCN1 (p=0.003-0.05). STAT4_rs7574865 TT was associated with the presence of actively inflamed joints [odds ratio (OR) 20.6, 95% confidence interval (CI) 2.2->100, p=0.003] and extra-articular damage (OR 7.9, 95% CI 1-56.6, p=0.057). ADAD1_rs17388568 AA was associated with a lower risk of having joints with LOM (OR 0.1, 95% CI 0-0.55, p=0.016). PTPN2_rs1893217 CC was associated with a lower risk of having joints with LOM (OR 0.2, 95% CI 0-0.99, p=0.026), while VTCN1_rs2358820 GA was associated with uveitis (OR 3.5, 95% CI 1-12.1, p=0.029).This exploratory study, using a prospectively followed JIA cohort, found significant associations between long-term outcome and SNPs, all previously associated with development of JIA and involved in immune regulation and signal transduction in immune cells.
3.	Arnstad, Ellen Dalen, et al. (författare) Early Self-Reported Pain in Juvenile Idiopathic Arthritis as Related to Long-Term Outcomes : Results From the Nordic Juvenile Idiopathic Arthritis Cohort Study 2019 Ingår i: Arthritis care & research. - : WILEY. - 2151-464X .- 2151-4658. ; 71:7, s. 961-969 Tidskriftsartikel (refereegranskat)abstract Objective To study self-reported pain early in the disease course of juvenile idiopathic arthritis (JIA) as a predictor of long-term disease outcomes. Methods Consecutive cases of JIA with disease onset from 1997 to 2000 from defined geographical areas of Norway, Sweden, Finland, and Denmark were prospectively enrolled in this population-based cohort study. Self-reported, disease-related pain was measured on a 10-cm visual analog scale (VAS pain). Inclusion criteria were a baseline visit with a pain score 6 months after disease onset, followed by an 8-year study visit. Remission was defined according to Wallace et al (2004) preliminary criteria. Functional disability was measured by the Childhood Health Assessment Questionnaire and the Child Health Questionnaire Parent Form if the child was age <18 years and by the Health Assessment Questionnaire if age >= 18 years. Damage was scored using the Juvenile Arthritis Damage Index. Results The final study cohort consisted of 243 participants, and 120 participants (49%) had oligoarticular onset. At baseline, 76% reported a VAS pain score >0 compared to 57% reporting at 8 years. Half of those who reported baseline pain also reported pain at 8 years but at a lower intensity. Compared to no pain, higher pain intensity at baseline predicted more pain at 8 years, more functional disability, more damage, and less remission without medication. Baseline pain predicted more use of disease-modifying antirheumatic drugs/biologics during the disease course. Participants with oligoarticular JIA reporting pain at baseline were more likely to develop extended oligoarticular JIA or other JIA categories with an unfavorable prognosis. Conclusion Early self-reported, disease-related pain among children and adolescents with JIA is common and seems to predict persistent pain and unfavorable long-term disease outcomes.
4.	Arnstad, Ellen Dalen, et al. (författare) Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset : data from the prospective Nordic JIA cohort 2021 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background To study fatigue in young adults with juvenile idiopathic arthritis (JIA) 18 years after disease onset, and to compare with controls. Methods Consecutive children with onset of JIA between 1997 and 2000, from geographically defined areas of Norway, Sweden, Denmark and Finland were followed for 18 years in a close to population-based prospective cohort study. Clinical features, demographic and patient-reported data were collected. Inclusion criteria in the present study were a baseline visit 6 months after disease onset, followed by an 18-year follow-up with available self-reported fatigue score (Fatigue Severity Scale (FSS), 1-7). Severe fatigue was defined as FSS >= 4. For comparison, Norwegian age and sex matched controls were used. Results Among 377 young adults with JIA, 26% reported severe fatigue, compared to 12% among controls. We found higher burden of fatigue among participants with sleep problems, pain, poor health, reduced participation in school/work, physical disability, active disease, or use of disease-modifying anti-rheumatic drugs (DMARDs)/biologics/systemic steroids. In contrast, participants without these challenges, had fatigue scores similar to controls. Active disease assessed at all three time points (baseline, 8-year and 18-year follow-up) was associated with higher mean fatigue score and higher percentage of severe fatigue compared to disease courses characterized by periods of inactive disease. Predictors of fatigue at the 18-year follow-up were female sex and diagnostic delay of >= 6 months at baseline, and also pain, self-reported poor health, active disease, and previous/ongoing use of DMARDs/biologics at 8 years. Conclusions Fatigue is a prominent symptom in young adults with JIA, with higher fatigue burden among participants with poor sleep, pain, self-reported health problems, active disease, or use of DMARDs/biologics. Participants without these challenges have results similar to controls. Patient- and physician-reported variables at baseline and during disease course predicted fatigue at 18-year follow-up.
5.	Arvonen, Miika, et al. (författare) Gut microbiota-host interactions and juvenile idiopathic arthritis 2016 Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 14 Forskningsöversikt (refereegranskat)abstract Background: Juvenile idiopathic arthritis is the most common form of chronic arthritis in children. There is mounting evidence that the microbiota may influence the disease. Main body: Recent observations in several systemic inflammatory diseases including JIA have indicated that abnormalities in the contents of the microbiota may be factors in disease pathogenesis, while other studies in turn have shown that environmental factors impacting the composition of the microbiota, such as delivery mode and early exposure to antibiotics, affect the risk of chronic inflammatory diseases including JIA. Microbial alterations may predispose to JIA through a variety of mechanisms, including impaired immunologic development, alterations in the balances of pro- versus anti-inflammatory bacteria, and low-grade mucosal inflammation. Additional confirmatory studies of microbiota aberrations and their risk factors are needed, as well as additional mechanistic studies linking these alterations to the disease itself. Conclusions: The microbiota may influence the risk of JIA and other systemic inflammatory conditions through a variety of mechanisms. Additional research is required to improve our understanding of the links between the microbiota and arthritis, and the treatment implications thereof.
6.	Backlund, Malin, et al. (författare) A cross-sectional cohort study of the activity and turnover of neutrophil granulocytes in juvenile idiopathic arthritis 2021 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Tidskriftsartikel (refereegranskat)abstract Background: The inflammatory process in juvenile idiopathic arthritis (JIA) involves both the innate and the adaptive immune system. The turnover and activity of neutrophil granulocytes may be reflected by proteins secreted from primary or secondary granules and from the cytoplasm of sequestered cells. Our primary aim was to compare the levels of the secondary neutrophil granule protein human neutrophil lipocalin (HNL), in JIA patients and controls, and to explore a possible priming of neutrophils through parallel analyses in plasma and serum. A secondary aim was to relate the levels of HNL to two other well-studied leukocyte proteins, S100A8/A9 and myeloperoxidase (MPO), as well as to clinical aspects of JIA.Methods: The concentrations of the three biomarkers in serum, two of them also in plasma, were measured using enzyme-linked immunosorbent assay in 37 children with JIA without medical treatment, in high disease activity based on juvenile arthritis disease activity score 27 (JADAS27), 32 children on medical treatment, mainly in lower disease activity, and 16 healthy children. We assessed for differences between two groups using the Mann-Whitney U test, and used the Kruskal-Wallis test for multiple group comparisons. Spearman rank correlation, linear and multiple regression analyses were used for evaluation of associations between biomarker concentrations and clinical scores.Results: The concentrations of HNL and MPO in serum were significantly increased in children with JIA (p<0.001, p=0.002) compared with healthy children, but we found no difference in the plasma levels of HNL and MPO between children with JIA and controls. The serum concentrations of MPO and HNL were unaffected by medical treatment, but S100A8/A9 was reduced by medical treatment and correlated with JADAS27 in both univariate (r=0.58, p<0.001) and multivariate (r=0.59, p<0.001) analyses.Conclusions: Neutrophil granulocytes in children with JIA are primed to release primary and secondary granule proteins, without relation to medical treatment, whereas signs of increased turnover and sequestration of neutrophil granulocytes are reduced by treatment. Levels of neutrophil-originating proteins in serum most likely reflect underlying disease activities of JIA.
7.	Berntson, Lillemor, 1957-, et al. (författare) A Pilot Study Investigating Faecal Microbiota After Two Dietary Interventions in Children with Juvenile Idiopathic Arthritis 2022 Ingår i: Current Microbiology. - : Springer Science and Business Media LLC. - 0343-8651 .- 1432-0991. ; 79:7 Tidskriftsartikel (refereegranskat)abstract There is evidence for an impact of the gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN) and the specific carbohydrate diet (SCD) have been demonstrated as effective anti-inflammatory treatments for children with Crohn’s disease. We have previously shown an anti-inflammatory effect from these nutritional treatments in children with juvenile idiopathic arthritis (JIA). The aim of this study was to investigate if improved clinical symptoms after EEN or SCD treatment in children with JIA could be linked to changes in faecal microbiota. We included sixteen patients with JIA (age 7–17 years), six for treatment with EEN and ten with SCD. EEN was given for 3–5 weeks and SCD for 4–5 weeks, with clinical and laboratory status assessed before and after treatment. Faecal samples were analysed for microbiota diversity and composition using 16S rRNA gene sequencing. Analyses of the faecal microbiota showed an effect on the overall composition with both interventions; the most striking result was a decreased relative abundance of the genus Faecalibacterium from EEN and of Bifidobacterium from SCD. The α-diversity decreased significantly from SCD (P = 0.04), but not from EEN (P = 0.22). Despite the study cohorts being small, both EEN and SCD were shown to impact the faecal microbiota. Future larger studies with a focus on metagenomics or metabolomics could possibly reveal a link and clarify the clinical effects of those nutritional regimens.
8.	Berntson, Lillemor, 1957- (författare) A pilot study of possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis 2021 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Tidskriftsartikel (refereegranskat)abstract BackgroundTo explore possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis. This diet has shown anti-inflammatory effect in children with inflammatory bowel disease.MethodsTwenty-two patients with juvenile idiopathic arthritis (age 6.3–17.3 years), with ≤2 inflamed joints and an erythrocyte sedimentation rate < 30 mm/h, were included in this explorative study. Fifteen children completing four weeks on the diet were evaluated. A dietician introduced parents and children to the diet, and two follow-ups were performed during the intervention. Conventional laboratory tests and multiplex analyses of 92 inflammatory proteins were used. Short-chain fatty acids in faecal samples were examined.ResultsThe diet significantly decreased morning stiffness (p = 0.003) and pain (p = 0.048). Physical function, assessed through the child health assessment questionnaire, improved (p = 0.022). Arthritis improved in five of the seven children with arthritis; in those seven, multiplex analyses showed a significant decrease in nine inflammatory proteins, including TNF-alpha (p = 0.028), after four weeks. Faecal butyrate, analysed in all 15 participants, increased significantly (p = 0.020).ConclusionThe specific carbohydrate diet may have significant positive effects on arthritis in children with juvenile idiopathic arthritis, but further studies are needed.
9.	Berntson, Lillemor (författare) Anti-inflammatory effect by exclusive enteral nutrition (EEN) in a patient with juvenile idiopathic arthritis (JIA) : brief report 2014 Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 33:8, s. 1173-1175 Tidskriftsartikel (refereegranskat)abstract There is extensive evidence for influence of gut microbiota on health. Exclusive enteral nutrition (EEN) possibly changes gut microbiota, but the exact pathophysiological role is unknown. EEN has been shown to have an anti-inflammatory effect in children with Mb Crohn, an inflammatory bowel disease. The intestinal tract is very scarcely studied in children with juvenile idiopathic arthritis (JIA), but data points to an immunologically important role. The aim of this study was to explore if EEN had any anti-inflammatory effect in children with JIA. The first patient enrolled in the study was followed for 1 year. She had onset of severe polyarticular disease at 3.2 years of age, negative in RF, anti-CCP, ANA, and HLA-B27. She was included in the study at 7.4 years of age. Exclusive enteral nutrition was given in two periods of almost 7 weeks each, several months apart, during the year of the study. Clinical and laboratory status were assessed before, during, and after treatment periods. In this patient, EEN had remarkable anti-inflammatory effect that was sustained for months after each of two separate treatment periods. Exclusive enteral nutrition is a possible anti-inflammatory treatment in patients with JIA, but to what extent EEN is effective in other children with JIA needs to be explored, as well as the possible pathophysiological role of EEN in those children.
10.	Berntson, Lillemor, et al. (författare) Anti-inflammatory effect of exclusive enteral nutrition in patients with juvenile idiopathic arthritis 2016 Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 34:5, s. 941-945 Tidskriftsartikel (refereegranskat)abstract Objective There is extensive evidence for an influence of gut microbiota on the immune system, which has consequences for inflammatory diseases. Exclusive enteral nutrition (EEN), which may change the gut microbiota, is an effective anti-inflammatory treatment for Crohn's disease in children. We wanted to explore the immediate anti-inflammatory effect of EEN in children with juvenile idiopathic arthritis (JIA). Methods Thirteen patients with JIA (7-17 years of age), in a disease flare-up, were included in the study. Six children dropped out within 1.5-2.0 weeks of treatment, and seven patients continued, constituting the study cohort. EEN was given for three to eight weeks, with clinical and laboratory status assessed before and after treatment periods. In addition to conventional laboratory tests, 92 inflammatory proteins were analysed with a multiplex system (Proseek Multiplex Inflammation I, Olink Bioscience). Results EEN had a significant anti-inflammatory effect on active joints (p=0.031), JADAS27 (p=0.016) and morning stiffness (p=0.031). In the multiplex analysis of inflammatory proteins, MMP-1 (matrix metalloproteinase), involved in the degradation of collagens in chondrocytes, decreased significantly (p=0.047), as did MCP-4 (p=0.031) and 4E-BP1 (p=0.031). Conclusion Exclusive enteral nutrition for three to eight weeks had anti-inflammatory effect in all children with JIA that continued with EEN for more than two weeks. The study is only exploratory but the result supports an immunologically important role for the intestinal canal in these patients.
11.	Berntson, Lillemor, et al. (författare) Anti-type II collagen antibodies, anti-CCP, IgA RF and IgM RF are associated with joint damage, assessed eight years after onset of juvenile idiopathic arthritis (JIA) 2014 Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12, s. 22- Tidskriftsartikel (refereegranskat)abstract Background: Early appearance of antibodies specific for native human type II collagen (anti-CII) characterizes an early inflammatory and destructive phenotype in adults with rheumatoid arthritis (RA). The objective of this study was to investigate the occurrence of anti-CII, IgM RF, IgA RF and anti-CCP in serum samples obtained early after diagnosis, and to relate the occurrence of autoantibodies to outcome after eight years of disease in children with juvenile idiopathic arthritis (JIA). Methods: The Nordic JIA database prospectively included JIA patients followed for eight years with data on remission and joint damage. From this database, serum samples collected from 192 patients, at a median of four months after disease onset, were analysed for IgG anti-CII, IgM RF, IgA RF and IgG anti-CCP. Joint damage was assessed based on Juvenile Arthritis Damage Index for Articular damage (JADI-A), a validated clinical instrument for joint damage. Results: Elevated serum levels of anti-CII occurred in 3.1%, IgM RF in 3.6%, IgA RF in 3.1% and anti-CCP in 2.6% of the patients. Occurrence of RF and anti-CCP did to some extent overlap, but rarely with anti-CII. The polyarticular and oligoarticular extended categories were overrepresented in patients with two or more autoantibodies. Anti-CII occurred in younger children, usually without overlap with the other autoantibodies and was associated with high levels of C-reactive protein (CRP) early in the disease course. All four autoantibodies were significantly associated with joint damage, but not with active disease at the eight-year follow up. Conclusions: Anti-CII, anti-CCP, IgA RF and IgM RF detected early in the disease course predicted joint damage when assessed after eight years of disease. The role of anti-CII in JIA should be further studied.
12.	Berntson, Lillemor, et al. (författare) Assessment of disease activity in juvenile idiopathic arthritis. The number and the size of joints matter 2007 Ingår i: JOURNAL OF RHEUMATOLOGY. - 0315-162X .- 1499-2752. ; 34:10, s. 2106-2111 Tidskriftsartikel (refereegranskat)
13.	Berntson, Lillemor, 1957-, et al. (författare) Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis : a cross-sectional study 2024 Ingår i: Pediatric Rheumatology. - : Springer Nature. - 1546-0096. ; 22:1 Tidskriftsartikel (refereegranskat)abstract Background: Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity.Methods: EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0-57), and pain levels were measured using a visual analogue scale (VAS, 0-10 cm).Results: Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group.Conclusion: The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.
14.	Berntson, Lillemor, et al. (författare) Changes in fecal microbiota and metabolomics in a child with juvenile idiopathic arthritis (JIA) responding to two treatment periods with exclusive enteral nutrition (EEN) 2016 Ingår i: Clinical Rheumatology. - : Springer Science and Business Media LLC. - 0770-3198 .- 1434-9949. ; 35:6, s. 1501-1506 Tidskriftsartikel (refereegranskat)abstract The microbiome and immune system of the digestive tract are highly important in both health and disease. Exclusive enteral nutrition (EEN) is a common anti-inflammatory treatment in children with Crohn's disease in the European countries, and the mechanism is most likely linked to changes in the intestinal microbiome. In the present study, EEN was given in two treatment periods several months apart to a patient with very severe, disabling juvenile idiopathic arthritis (JIA), with a remarkable clinical response as the result. The aim of the present study was to study how the EEN treatment influenced the microbiome and metabolome of this patient. Fecal samples from before, during, and between treatments with EEN were studied. The microbiome was analyzed by sequencing of 16S rRNA amplicons using Illumina MiSeq, and the metabolome was analyzed using nuclear magnetic resonance. The microbiome changed markedly from treatment with EEN, with a strong reduction of the Bacteroidetes phylum. Metabolic profiles showed clear differences before, during, and between treatment with EEN, where butyrate, propionate, and acetate followed a cyclic pattern with the lowest levels at the end of each treatment period. This patient with JIA showed remarkable clinical improvement after EEN treatment, and we found corresponding changes in both the fecal microbiome and the metabolome. Further studies are needed to explore the pathophysiological role of the intestinal canal in children with JIA.
15.	Berntson, Lillemor, 1957, et al. (författare) God hjälp av modern behandling vid juvenil idiopatisk artrit. 2013 Ingår i: Läkartidningen. - 0023-7205. ; 110:15, s. 754-7 Tidskriftsartikel (refereegranskat)
16.	Berntson, Lillemor, 1957-, et al. (författare) Haptoglobin in Juvenile Idiopathic Arthritis 2022 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Haptoglobin (Hp), a liver derived acute phase inflammatory protein (APP), has scarcely been studied in juvenile idiopathic arthritis (JIA). Hp can occur in blood as two isoforms (Hp1 and Hp2) in precursor and mature forms. Routine clinical chemistry immunoturbidimetry does not discern these forms. It is unknown how different forms relate to disease activity in JIA. Our aims were to determine allele frequency and plasma concentrations of different Hp forms at higher versus lower JIA disease activity and compare to other APPs.METHODS: Plasma from JIA (n = 77) and healthy (n = 42) children were analyzed for apparent Hp allelic frequency and densitometric concentrations of alpha forms by Western blot (WB). Polymerase chain reaction (PCR) (buffy coat) was performed in a subset to estimate conformity with genetics. At higher versus lower juvenile arthritis disease activity score (JADAS27) (which includes erythrocyte sedimentation rate (ESR)), total mature Hp concentration from WB was compared and correlated against immunoturbidimetry and total protein, albumin, serum amyloid A (SAA) and C-reactive protein (CRP).RESULTS: At 300-fold dilution needed to study mature forms in Western blot, precursors were undetectable. Hp2 contributed most signal in most samples. Hp allele frequency was similar in JIA and controls. Both mature forms, taken separately or by sum, declined following treatment, but remained above concentrations of healthy controls, even in a remission subset that achieved JADAS27 < 1. Densitometry correlated with immunoturbidimetry. Hp concentrations correlated with JADAS27, albumin (negatively), CRP and SAA with immunoturbidimetric method correlating strongest to JADAS27 (Spearman R ~ 0.6, p < 0.0001).CONCLUSION: Hp allele frequency in JIA is similar to the general population, indicating that children with JIA should have the same possibility as in healthy children to produce preHp2 (zonulin), thought to increase intestinal permeability. Circulating Hp concentrations largely parallel other APPs and ESR; none of these measures correlate very strongly to JADAS27 score but Hp can be measured from capillary sampling which is impossible with ESR.
17.	Berntson, Lillemor, 1957-, et al. (författare) HLA-B27 Predicts a More Chronic Disease Course in an 8-year Followup Cohort of Patients with Juvenile Idiopathic Arthritis 2013 Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 40:5, s. 725-731 Tidskriftsartikel (refereegranskat)abstract Objective. We investigated associations of HLA-B27 with clinical manifestations and longterm outcome in a near population-based setting among patients with juvenile idiopathic arthritis (JIA). Methods. We studied clinical and serological data from 410 patients with HLA-B27 results among 440 prospectively collected patients with JIA with 8-year followup data in a Nordic database. The study was structured to be as close to a population-based study as possible. Results. HLA-B27 was analyzed in 93% of patients, and was positive in 21% of the cohort, in 18.4% of the girls and in 25.9% of the boys. Boys who were HLA-B27-positive had significantly higher age at onset compared to HLA-B27-negative boys and compared to both HLA-B27-negative and positive girls. This difference in onset age in relation to HLA-B27 was not found in girls. HLA-B27 was associated with clinical signs of sacroiliitis, enthesitis, and tenosynovitis in boys, but not in girls. After 8 years of disease, 46 children (11.2%) were classified as having enthesitis-related arthritis (ERA). Boys with ERA had clinical signs of sacroiliitis more often than girls with ERA. HLA-B27-positive children, as well as children with clinical signs of sacroiliitis, enthesitis, and hip arthritis, had higher odds of not being in remission off medication after 8 years of disease. Conclusion. In this near population-based Nordic JIA cohort we found significant differences between HLA-B27-positive boys and girls in age at disease onset, clinical signs of sacroiliitis, and ERA classification. HLA-B27 was negatively associated with longterm remission status, possibly because of its association with clinical disease characteristics, such as sacroiliitis, rather than being a general marker of persistent disease.
18.	Berntson, Lillemor, 1957-, et al. (författare) HLA-B27 predicts a more extended disease with increasing age at onset in boys with juvenile idiopathic arthritis 2008 Ingår i: British Journal of Rheumatology. - 0263-7103 .- 1460-2172 .- 0315-162X .- 1499-2752. ; 35:10, s. 2055-2061 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a heterogeneous condition with very few clinical and laboratory signs that can help predict the course and severity of the disease in the individual patient. The cell-surface antigen HLA-B27 is well known to be associated with spondyloarthropathies, reactive arthritis, and enthesitis. HLA-B27 plays an important role in the classification of JIA, since evidence of sacroiliitis most often evolves after years of arthritis in other joints. We investigated the associations of HLA-B27 and the clinical manifestations of JIA using a method as close to a population-based study as possible.METHODS: We studied an incidence-based cohort of 305 patients collected prospectively in 3 Nordic countries (Sweden, Norway, Denmark). Clinical and serological data of the first 3 years of the disease were collected.RESULTS: HLA-B27 was found to be positive in 25.5% of the patients, and we found a higher proportion of HLA-B27-positive boys with older age at disease onset (p=0.034). Regression analysis showed a correlation of 0.7 in the HLA-B27-positive boys, pointing to a higher risk of more joint involvement with older age at disease onset. By Fisher's exact test, involvement of small joints in the lower extremities was associated with HLA-B27 in boys (p=0.011), but not in girls (p=0.687). HLA-B27 was associated with inflammatory back pain in both sexes (p=0.041 in boys, p=0.042 in girls), but with enthesitis only in boys (p<0.001 in boys, p=0.708 in girls).CONCLUSION: HLA-B27 is of increasing importance with older age at disease onset in boys with JIA, predicting more active joints within the first 3 years of disease, and also involving small joints in the lower extremity to a greater degree than in HLA-B27-negative boys. During the first 3 years of disease the occurrence of HLA-B27 is associated with inflammatory back pain in both sexes, but with enthesitis only in boys. Our data present new challenges for the ILAR classification of JIA.
19.	Berntson, Lillemor, 1957 (författare) JIA (juvenile idiopathic arthritis) in the Nordic countries. Aspects of classification, epidemiology and pain assessment 2003 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Different classification criteria for chronic arthritis in childhood have been used in different parts of the world, which has made comparison between studies difficult. In 1995, a new set of classification criteria was proposed by the ILAR (International League of Associations for Rheumatism) to overcome such difficulties and to create more homogenous subgroups. A new name was proposed: juvenile idiopathic arthritis (JIA). This thesis took advantage of the homogeneity of the Nordic health care systems to study the epidemiology of chronic childhood arthritis in the Nordic countries and to evaluate the construct validity of the new ILAR criteria compared with the EULAR (European League Against Rheumatism) criteria, which were used in Europe previously. This prospective, population-based study had its origin in a group of Nordic pediatric rheumatologists and pediatricians and it was performed over an 18-month period, commencing on July 1st 1997. Twenty doctors collected data from the incidence cases in their area, collaborating continuously within the study group. A classification was made according to the EULAR and ILAR classification criteria and an evaluation was made of the differences in how the two sets of criteria work. Incidence figures according to both sets of criteria in the different catchment areas were studied as well as incidence of the subgroups of the disease. Heredity for psoriasis and its influence on the ILAR classification were also explored. In a separate study on how to measure and evaluate pain, 26 children and their parents were involved. The VAS (visual analogue scale) is the most commonly used pain scale as it is considered to be easy to use. But is also criticized for being difficult to interpret and an evaluation was made of VAS in comparison with the results obtained using a category scale. Use was also made of a statistical method designed for this type of study. The ILAR and EULAR criteria sets classify children differently and cannot replace each other. In the ILAR classification, 21% of the patients could not be classified into any specific subgroup, only into the "other arthritis" subgroup. The average annual incidence rate of JIA (ILAR criteria) in the Nordic countries was 15 (13-17) per 100,000 children under 16 years of age. It varied from 7 (95% confidence interval 1-13) to 23 (10-36) in different areas. The distribution of age of onset and of ANA-positivity was different for boys and girls, girls showing an early peak in incidence. Heredity for psoriasis has a strong influence on the current ILAR classification and 21% of the patients had heredity for psoriasis among first-degree relatives or second-degree relatives or both. In an assessment of pain, parents and children used the VAS and the VDS-4 differently and the results for VAS revealed considerable variation.Conclusions: The ILAR classification criteria are a promising instrument in the search for more biologically homogenous groups in chronic arthritis in childhood. Incidence figures in the Nordic countries were in accordance with earlier incidence figures and higher compared with other European countries. In the patient follow-up the results for VAS were difficult to interpret.
20.	Berntson, Lillemor, 1957-, et al. (författare) Severe Raynaud's phenomenon from ethosuximide raised concern over possible onset of systemic vasculitis : a case report 2022 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20 Tidskriftsartikel (refereegranskat)abstract Background: Ethosuximide and other anti-epileptic drugs have been reported to cause idiosyncratic reactions such as lupus-like syndromes, with elevated antinuclear antibody (ANA) levels. Herein, we present a case of a girl who developed a very severe Raynaud's phenomenon reaction and anti-Scl-70 antibodies related to treatment with ethosuximide, due to juvenile absence epilepsy (JAE).Case presentation: A 12-year-old girl was diagnosed with JAE and treatment with ethosuximide was initiated. Two and a half months later her fingers, digits II-V bilaterally, began to ache and were discolored, alternatingly white, blue, or normal-colored. Two weeks later, her fingers were bluish-black, aching severely, almost continuously. The family sought medical advice. Ethosuximide was halted and due to the severe symptoms, treatment with both prednisolone and intravenous iloprost was commenced. Laboratory tests revealed high ANA levels with anti-Scl-70 pattern and confirmed anti-Scl-70 antibodies. After a few weeks, she started to improve and the symptoms slowly decreased over five months. Anti-Scl-70 was still detectable four months after onset of symptoms, though she was much improved. After eleven months, repeated ANA analyses were completely negative.Conclusion: Although extremely rare, it is important to recognize that severe Raynaud's phenomenon, threatening peripheral digital circulation, may occur as an idiosyncratic reaction to ethosuximide, raising concern over possible onset of vasculitis.
21.	Beukelman, Timothy, et al. (författare) A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis : challenges and opportunities 2017 Ingår i: Pediatric Rheumatology. - : BIOMED CENTRAL LTD. - 1546-0096. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: To characterize the existing national and multi-national registries and cohort studies in juvenile idiopathic arthritis (JIA) and identify differences as well as areas of potential future collaboration.Methods: We surveyed investigators from North America, Europe, and Australia about existing JIA cohort studies and registries. We excluded cross-sectional studies. We captured information about study design, duration, location, inclusion criteria, data elements and collection methods.Results: We received survey results from 18 studies, including 11 national and 7 multi-national studies representing 37 countries in total. Study designs included inception cohorts, prevalent disease cohorts, and new treatment cohorts (several of which contribute to pharmacosurveillance activities). Despite numerous differences, the data elements collected across the studies was quite similar, with most studies collecting at least 5 of the 6 American College of Rheumatology core set variables and the data needed to calculate the 3-variable clinical juvenile disease activity score. Most studies were collecting medication initiation and discontinuation dates and were attempting to capture serious adverse events.Conclusion: There is a wide-range of large, ongoing JIA registries and cohort studies around the world. Our survey results indicate significant potential for future collaborative work using data from different studies and both combined and comparative analyses.
22.	Brix, Ninna, et al. (författare) Inflammatory Biomarkers Can Differentiate Acute Lymphoblastic Leukemia with Arthropathy from Juvenile Idiopathic Arthritis Better Than Standard Blood Tests 2023 Ingår i: The Journal of Pediatrics. - : Elsevier. - 0022-3476 .- 1097-6833. ; 258 Tidskriftsartikel (refereegranskat)abstract Objective: To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).Study design: In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n = 150, including 27 with arthropathy) and JIA (n = 236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.Results: In ALL, the levels of S100A9, S100A12, interleukin (IL)-1 beta, IL-4, IL-13, IL-17, matrix metalloproteinase-3, and myeloperoxidase were low compared with JIA (P < .001). IL-13 had an AUC of 100% (95% CI 100%-100%) due to no overlap between the serum levels in the 2 groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97%-100%) and 98% (95% CI 94%-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.Conclusions: The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.
23.	Brix, Ninna, et al. (författare) Inflammatory Biomarkers Can Differentiate ALL with Arthropathy from JIA Better Than Standard Blood Tests. 2023 Ingår i: The Journal of pediatrics. - 1097-6833. ; 258 Tidskriftsartikel (refereegranskat)abstract To evaluate the predictive value of biomarkers of inflammation like phagocyte-related S100 proteins and a panel of inflammatory cytokines in order to differentiate the child with acute lymphoblastic leukemia (ALL) from juvenile idiopathic arthritis (JIA).In this cross-sectional study, we measured S100A9, S100A12, and 14 cytokines in serum from children with ALL (n=150, including 27 with arthropathy) and JIA (n=236). We constructed predictive models computing areas under the curve (AUC) as well as predicted probabilities in order to differentiate ALL from JIA. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated 10-fold cross-validation and recalibration, adjusted for age.In ALL, the levels of S100A9, S100A12, IL-1 beta, IL-4, IL-13, IL-17, MMP-3, and MPO were low compared with JIA (p <0.001). IL-13 had an AUC of 100% (95% CI 100-100%) due to no overlap between the serum levels in the two groups. Further, IL-4 and S100A9 had high predictive performance with AUCs of 99% (95% CI 97-100%) and 98% (95% CI 94-99%), respectively, exceeding both hemoglobin, platelets, C-reactive protein, and erythrocyte sedimentation rate.The biomarkers S100A9, IL-4, and IL-13 might be valuable markers to differentiate ALL from JIA.
24.	Brix, Ninna, et al. (författare) M-ficolin: a valuable biomarker to identify leukaemia from juvenile idiopathic arthritis. 2022 Ingår i: Archives of disease in childhood. - : BMJ. - 1468-2044 .- 0003-9888. ; 107:4, s. 371-376 Tidskriftsartikel (refereegranskat)abstract Distinction on clinical grounds between acute lymphoblastic leukaemia presenting with arthropathy (ALLarthropathy) and juvenile idiopathic arthritis (JIA) is difficult, as the clinical and paraclinical signs of leukaemia may be vague. The primary aim was to examine the use of lectin complement pathway proteins as markers to differentiate ALLarthropathy from JIA. The secondary aims were to compare the protein levels at baseline and follow-up in a paired number of children with ALL and to examine the correlation with haematology counts, erythrocyte sedimentation reaction (ESR), C-reactive protein (CRP), blasts, relapse and death.In this observational study, we measured M-ficolin, CL-K1 and MASP-3 in serum from children with ALL (n=151) and JIA (n=238) by time-resolved immunofluorometric assays. Logistic regression was used for predictions of ALL risk, considering the markers as the respective exposures. We performed internal validation using repeated '10-fold cross-validation' with 100 repetitions computing the area under the curve (AUC) as well as positive and negative predictive values in order to evaluate the predictive performance.The level of M-ficolin was higher in JIA than ALLtotal and the ALLarthropathy subgroup. The M-ficolin level normalised after remission of ALL. M-ficolin could differentiate ALL from JIA with an AUC of 94% and positive predictive value (PPV) of 95%, exceeding CRP and haemoglobin. In a dichotomised predictive model with optimal cut-offs for M-ficolin, platelets and haemoglobin, AUC was 99% and PPV 98% in detecting ALL from JIA.M-ficolin is a valuable marker to differentiate the child with ALL from JIA.
25.	Cedströmer, Anna-Lena, 1974, et al. (författare) Condylar alterations and facial growth in children with juvenile idiopathic arthritis 2020 Ingår i: Journal of Orofacial Orthopedics-Fortschritte Der Kieferorthopadie. - : Springer Science and Business Media LLC. - 1434-5293 .- 1615-6714. ; 81, s. 163-171 Tidskriftsartikel (refereegranskat)abstract Purpose The aim of this retrospective study was to evaluate facial growth in children with juvenile idiopathic arthritis (JIA) by means of lateral head cephalometric radiographs and relate the findings to temporomandibular joint (TMJ) condylar changes on panoramic radiographs. Methods Radiographic and medical records were evaluated in 65 children with JIA. Cephalometric and panoramic analyses were performed for the impact of condylar changes on facial growth. We compared children with condylar alterations, minor or major, with those without condylar alterations. Results Based on panoramic radiographs, no condylar alterations were seen in 27 of the 65 children and condylar alterations were seen in 38 children (i.e., 23 had minor and 15 major condylar alterations). The cephalometric analyses of the children with condylar changes showed significant growth disturbances with a more retrognathic mandible (SNB; p& x202f;= 0.03), retruded chin position (SNPog; p& x202f;= 0.02), larger mandibular angulation (ML/NSL; p& x202f;= 0.009) and maxillary angulation (NL/NSL; p& x202f;= 0.03) compared with children without condylar alterations. Children with minor condylar alterations had a significantly more retruded chin position (SNPog) than those with no condylar changes (p& x202f;= 0.04). Conclusions Condylar changes in the TMJ, judged on panoramic radiography, in children with JIA, have impact on craniofacial growth. Even minor alterations seem to have an impact.
26.	Cedströmer, Anna-Lena, 1974, et al. (författare) Temporomandibular condylar alterations in juvenile idiopathic arthritis most common in longitudinally severe disease despite medical treatment 2014 Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12 Tidskriftsartikel (refereegranskat)abstract Background: Juvenile idiopathic arthritis (JIA) is an autoimmune, heterogeneous disease and the temporomandibular joint (TMJ) can be affected, with consequences for mandibular growth and function. The aim of this study was to evaluate the importance of longitudinal medical treatment and the burden of disease activity on the development of temporomandibular condylar alterations as judged on panoramic radiographs. Methods: The study was a retrospective evaluation of dental and medical records in consecutive JIA patients referred to three specialist dental clinics in Sweden during an eight-year period. Data on the total pharmacological treatment and disease activity were evaluated longitudinally from disease onset to the time of the panoramic examination, during a median observation period of 2.5 years. The radiographs were analysed in terms of structural and shape alterations in the condyles and judged dichotomously. Results: Panoramic examinations were analysed in 158 patients from 266 referrals diagnosed with JIA. Condylar alterations (shape or structural) were seen in 68 patients (43%). Patients with condylar alterations were more extensively treated over time compared with those without condylar alterations. Powerful disease activity and/or potent medication at any time during the course of the disease implied an increased risk of alterations. Conclusions: Patients with JIA who require more intensive medication over time run the greatest risk of condylar alterations. As yet, current medical programmes have not been specified for the TMJ and more knowledge in this area is needed.
27.	Cedströmer, Anna-Lena, 1974, et al. (författare) Temporomandibular signs, symptoms, joint alterations and disease activity in juvenile idiopathic arthritis – an observational study 2013 Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 11:37 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease that frequently affects also the temporomandibular joint (TMJ) and associated structures. The main aim of this observational study was to describe systematically orofacial clinical signs and subjective symptoms in JIA patients, classified according to the International League of Associations for Rheumatology (ILAR) criteria, and to relate the findings to disease activity and radiological TMJ condyle lesions. METHODS: The study was a retrospective evaluation of dental and medical records in consecutive JIA patients referred to one of three dental specialist clinics in Sweden during an eight-year period. Data concerning temporomandibular signs, symptoms and general disease activity were collected and condylar alterations were judged on panoramic radiographs. RESULTS: All ILAR categories of JIA were represented among the 266 referrals included in the study. The distribution of patients among categories resembled the pattern seen in epidemiological studies. Persistent oligoarthritis was the largest category with 36.5 % of the patients. Temporomandibular clinical signs (mild, moderate or severe) occurred in 57.7 % to 92.0 %, and subjective symptoms (mild or severe) in 32.0 % to 76.0 % of the patients in all categories. Patients in the juvenile psoriatic arthritis category had the largest number of orofacial signs and symptoms, and patients in the persistent oligoarthritis category had the fewest signs and symptoms. There were significant associations between clinical signs as well as subjective symptoms and overall disease activity. Half of all the patients had undergone panoramic examinations and 37.9 % of those were judged to have condylar alterations after a mean of 2.9 years after onset. No associations between radiological findings and variables, such as signs, symptoms or disease activity, were found. CONCLUSIONS: Temporomandibular signs and symptoms can be expected to a varying degree, including severe cases, in all JIA categories. Clinical and subjective orofacial involvement appears to be related to disease activity but not to condylar lesions.
28.	Dahlbom, Ingrid, et al. (författare) Simultaneous detection of IgA and IgG antibodies against tissue transglutaminase : The preferred pre-biopsy test in childhood celiac disease 2016 Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 76:3, s. 208-216 Tidskriftsartikel (refereegranskat)abstract Objectives: IgA antibodies against tissue transglutaminase (anti-TG2) is a reliable marker of celiac disease (CD). However, IgA-deficient patients are not identified and young children may lack IgA anti-TG2. Combined detection of IgA and IgG (IgA/IgG) against deamidated gliadin peptides (DGP) has shown a high diagnostic performance for untreated CD. Here we examined the utility of IgA/IgG anti-TG2, IgA/IgG anti-DGP and IgA/IgG against a mix of TG2 and DGP (anti-TG2/DGP) in finding CD among children.Methods: Serum antibodies against TG2, DGP, and TG2/DGP were determined with ELISA in 242 children referred to a paediatric gastroenterologist. Fifty had untreated CD verified by an intestinal biopsy and 192/242 children had other diseases than CD.Results: Forty-eight untreated CD children had increased IgA/IgG anti-TG2, 47/50 had increased IgA/IgG anti-DGP and 46/50 had increased IgA/IgG anti-TG2/DGP. One control subject had increased IgA/IgG anti-TG2 and IgA/IgG anti-TG2/DGP, whereas 7/192 control subjects had increased IgA/IgG anti-DGP. The IgA/IgG anti-TG2 assay had the best performance with a sensitivity of 96%, a specificity of 99.5% and the area under the ROC-curve was 0.996 (95% CI 0.992-1, p < 0.0001).Conclusions: Detection of one antibody is not sufficient when screening for untreated CD among children due to cases of IgA deficiency. The inclusion of DGP antigens in the IgA/IgG combination assays seems to affect the sensitivity and specificity negatively, whereas detection of IgA/IgG anti-TG2 has the potential of finding most untreated CD patients, including those with IgA deficiency.
29.	Ekelund, Maria, et al. (författare) Psoriasis and associated variables in classification and outcome of juvenile idiopathic arthritis - an eight-year follow-up study 2017 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 15 Tidskriftsartikel (refereegranskat)abstract Background: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA). Methods: In all, 440 children with JIA were followed for a median of 8 years in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission. Results: Clinical findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we found a cumulative median number of eleven arthritic joints in children with psoriasis or psoriasis- like rash compared with six in the rest of the cohort (p = 0.02). Also, the chance for not being in remission after 8 years increased significantly in patients with psoriasis, psoriasis-like rash or at least two of: 1) first-degree heredity for psoriasis or psoriatic arthritis, 2) dactylitis or 3) nail pitting, compared with the rest of the group (OR 3.32, p = 0.010). Conclusions: Our results indicate a more severe disease over time in psoriasis- associated JIA, as features of psoriasis develop during the disease course. This group is a major challenge to encompass in a future JIA classification in order to facilitate early tailored treatment.
30.	Ekelund, Maria, 1970- (författare) Psoriasis and Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis (JIA) : A Longitudinal Study of the Nordic JIA Cohort 2020 Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract Juvenile idiopathic arthritis, JIA, is used as an umbrella term covering a heterogeneous group of chronic arthritis forms in children, many of which have important differences compared to adult arthritis, while others possibly represent similar diseases among children and adults. Classification aims to give a better understanding of the pathogenesis, patterns, disease trajectories and treatment responses. For the juvenile psoriatic arthritis, JPsA, the classification criteria are currently being debated. The distribution of affected joints in JIA differs greatly and it is unknown why some joints appear to be more affected than others. The temporomandibular joint (TMJ) can be affected early in the course of the disease and often the symptoms are mild and without obvious swelling.This thesis has its origin in the Nordic Study Group of Paediatric Rheumatology and the population-based prospective study of 510 children with newly diagnosed JIA included between 1997 and 1999. Totally 440 children were included in the eight-year follow-up, and in the TMJ study 265 patients were examined and underwent cone-beam computed tomography, CBCT, 17 years after onset.After eight years a considerable proportion of the children with definite psoriasis were classified as undifferentiated JIA based on the exclusion criteria in the ILAR classification. Our data also presents the heterogenicity of JPsA and the development over time of clinical variables supporting a psoriatic diathesis, as well as the overlap between JPsA and enthesitis-related arthritis in a group of patients. We found that extensive symptoms and dysfunctions of the TMJ are seen in JIA 17 years after disease onset, even in patients registered with inactive disease or remission. Individuals with substantial condylar damage on CBCT were found in all JIA categories. The deeper understanding of a chronic disease over time is crucial for research initiatives to improve care as well as for clinical decisions and planning of the health care.Our findings suggest a need for a more appropriate classification of JPsA and also that aspects of TMJ involvement should be included in the general health assessment in JIA.
31.	Ekelund, Maria, et al. (författare) The Swedish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR) 2018 Ingår i: Rheumatology International. - : SPRINGER HEIDELBERG. - 0172-8172 .- 1437-160X. ; 38:Suppl. 1, s. 371-377 Tidskriftsartikel (refereegranskat)abstract The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Swedish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 68 JIA patients (8.8% systemic, 44.1% oligoarticular, 13.2% RF negative polyarthritis, 33.9% other categories) and 76 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Swedish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.
32.	Elfving, Andreas, et al. (författare) An explorative study on proteomic analyses related to inflammation and pain in children with juvenile idiopathic arthritis 2023 Ingår i: BMC Pediatrics. - : Springer Nature. - 1471-2431. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Background: Our aim was attempting to find proteins involved in the pain process and correlating with pain but not degree of inflammation in children with juvenile idiopathic arthritis (JIA), using a proteomics panel.Methods: A total of 87 plasma samples were collected from 51 children with JIA (51 at diagnosis in a higher disease activity state, 18 at follow-up in a lower disease activity state) and 18 healthy controls. Relative levels of 92 proteins related to a wide range of biological processes in inflammation were obtained using a proximity extension assay panel. Comparisons between children with and without JIA, in different disease categories, by juvenile disease activity score (JADAS27) and degree of pain on a visual analogue scale (VAS), were performed using parametric and non-parametric statistical methods.Results: Nineteen proteins involved in arthritic inflammation, such as interleukin 6 (IL-6) and S100 protein A12, were higher in patients with JIA than controls, seven decreased significantly during treatment, and 18 correlated significantly with JADAS27. Three proteins correlated with pain VAS scores in unadjusted analyses: the glial cell line-derived neurotrophic factor (GDNF), transforming growth factor beta, and IL-18R1. Levels of GDNF correlated significantly with pain VAS scores but not with JADAS27.Conclusions: Plasma levels of 18 of 92 tested proteins correlated with degree of disease activity. Levels of three proteins correlated with pain, and levels of one, GDNF, originating from neural cells, correlated with pain without correlating with inflammatory degree, suggesting that it may play a role in pain in JIA. Further studies in larger cohorts are warranted.
33.	Esbjornsson, A-C, et al. (författare) Ankle arthritis predicts polyarticular disease course and unfavourable outcome in children with juvenile idiopathic arthritis 2015 Ingår i: Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 33:5, s. 751-757 Tidskriftsartikel (refereegranskat)abstract Objective To evaluate the occurrence, clinical characteristics and prognostic factors associated with ankle arthritis in children with juvenile idiopathic arthritis (JIA). Methods 440 children with JIA were followed for eight years in a prospective Nordic population-based cohort study. Data on remission was available for 427 of these children. Occurrence of clinically assessed ankle arthritis was analysed in relation to JIA category, clinical characteristics and remission data eight years after disease onset. Results In 440 children with JIA, 251 (57%) experienced ankle arthritis during the first eight years of disease. Ankle arthritis was least common in the persistent oligoarticular category (25%) and most common in children with extended oligoarticular (83%) and polyarticular RF-negative (85%) JIA. Children who developed ankle arthritis during the first year of disease were younger at disease onset (median age 4.9 (IQR 2.1-8.8) vs. 6.6 (IQR 2.8-10.1) years, p<0.003) and had more cumulative affected joints at 8-year follow-up (median involved joints 10 (IQR 6-16) vs. 3 (IQR 2-9), p<0.001). The odds ratio for not achieving remission eight years after disease onset, if the ankle joint was involved during the first year of disease was 2.0 (95 %.0, p<0.001). Hind-, mid- and forefoot involvements were more common compared to patients without ankle arthritis. Conclusion In this Nordic population-based 8-year follow-up study, occurrence of ankle arthritis during the first year was associated with an unfavourable disease outcome. We suggest that ankle arthritis should be recognised in the assessment of prognosis and choice of treatment strategy in JIA.
34.	Foeldvari, Ivan, et al. (författare) After 24 Months Observation Period the Patients Related Outcomes Improve Significantly in the Juvenile Scleroderma Inceptions Cohorte 2018 Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
35.	Foeldvari, Ivan, et al. (författare) Differences Sustained Between Diffuse and Limited Forms of Juvenile Systemic Sclerosis in an Expanded International Cohort 2022 Ingår i: Arthritis care & research. - : John Wiley & Sons. - 2151-464X .- 2151-4658. ; 74:10, s. 1575-1584 Tidskriftsartikel (refereegranskat)abstract Objective To evaluate the baseline clinical characteristics of juvenile systemic sclerosis (SSc) patients in the international juvenile SSc inception cohort, and to compare these characteristics between the classically defined juvenile diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) subtypes and among those with overlap features. Methods A cross-sectional study was performed using baseline visit data. Information on demographic characteristics, organ system evaluation, treatment, and patient- and physician-reported outcomes was extracted and summary statistics applied. Comparisons between juvenile dcSSc and lcSSc subtypes and patients with and without overlap features were performed using chi-square and Mann-Whitney U tests. Results At data extraction, 150 juvenile SSc patients were enrolled across 42 centers; 83% were White, 80% were female, juvenile dcSSc predominated (72%), and 17% of the cohort had overlap features. Significant differences were found between juvenile dcSSc and juvenile lcSSc regarding modified Rodnan skin thickness score, the presence of Gottron's papules, digital tip ulceration, results of the 6-minute walk test, and composite pulmonary and cardiac involvement. All of these were more frequent in dcSSc except for cardiac involvement. Juvenile dcSSc patients had significantly worse scores for physician-rated disease activity and damage. A significantly higher occurrence of Gottron's papules and musculoskeletal and composite pulmonary involvement, and a significantly lower frequency of Raynaud's phenomenon, were seen in those with overlap features. Conclusion Results from a large international juvenile SSc cohort demonstrate significant differences between juvenile dcSSc and juvenile lcSSc patients, including more globally severe disease and increased frequency of interstitial lung disease in juvenile dcSSc patients, while those with lcSSc have more frequent cardiac involvement. Those with overlap features had an unexpected higher frequency of interstitial lung disease.
36.	Foeldvari, Ivan, et al. (författare) Gender differences in juvenile systemic sclerosis patients : Results from the international juvenile scleroderma inception cohort 2023 Ingår i: Journal of Scleroderma and Related Disorders. - : Sage Publications. - 2397-1983 .- 2397-1991. ; 8:2, s. 120-130 Tidskriftsartikel (refereegranskat)abstract Objective: To compare organ involvement and disease severity between male and female patients with juvenile onset systemic sclerosis.Methods: Demographics, organ involvement, laboratory evaluation, patient-reported outcomes and physician assessment variables were compared between male and female juvenile onset systemic sclerosis patients enrolled in the prospective international juvenile systemic sclerosis cohort at their baseline visit and after 12 months.Results: One hundred and seventy-five juvenile onset systemic sclerosis patients were evaluated, 142 females and 33 males. Race, age of onset, disease duration, and disease subtypes (70% diffuse cutaneous) were similar between males and females. Active digital ulceration, very low body mass index, and tendon friction rubs were significantly more frequent in males. Physician global assessment of disease severity and digital ulcer activity was significantly higher in males. Composite pulmonary involvement was also more frequent in males, though not statistically significantly. After 12 months, they are the pattern of differences changed female patients had significantly more frequent pulmonary involvement.Conclusion: In this cohort, juvenile onset systemic sclerosis had a more severe course in males at baseline and but the pattern changed after 12 months. Some differences from adult findings persisted, there is no increased signal of pulmonary arterial hypertension or heart failure in male pediatric patients. While monitoring protocols of organ involvement in juvenile onset systemic sclerosis need to be identical for males and females.
37.	Foeldvari, Ivan, et al. (författare) Underdetection of Interstitial Lung Disease in Juvenile Systemic Sclerosis 2022 Ingår i: Arthritis care & research. - : John Wiley & Sons. - 2151-464X .- 2151-4658. ; 74:3, s. 364-370 Tidskriftsartikel (refereegranskat)abstract Objective. Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. Methods. The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of P FT parameters, FVC, and DLco in detecting ILD. Results. Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. Conclusion. The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss -60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.
38.	Foeldvari, Ivan, et al. (författare) Update from the Juvenile Scleroderma Inception Cohort 2018 Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
39.	Foell, Dirk, et al. (författare) A novel serum calprotectin (MRP8/14) particle-enhanced immuno-turbidimetric assay (sCAL turbo) helps to differentiate systemic juvenile idiopathic arthritis from other diseases in routine clinical laboratory settings 2023 Ingår i: Molecular and Cellular Pediatrics. - : Springer. - 2194-7791. ; 10 Tidskriftsartikel (refereegranskat)abstract Background: Differential diagnosis in children with signs of unprovoked inflammation can be challenging. In particular, differentiating systemic juvenile idiopathic arthritis (SJIA) from other diagnoses is difficult. We have recently validated the complex of myeloid-related proteins 8/14 (MRP8/14, also known as S100A8/A9 complex or serum calprotectin) as a helpful biomarker supporting the diagnosis of SJIA. The results were subsequently confirmed with a commercial ELISA. However, further optimization of the analytical technology is important to ensure its feasibility for large-scale use in routine laboratory settings.Methods: To evaluate the accuracy in identifying children with SJIA, the performance of a particle-enhanced immuno-turbidimetric assay for serum calprotectin (sCAL turbo) on an automated laboratory instrument was analyzed. Samples from 615 children were available with the diagnoses SJIA (n = 99), non-systemic JIA (n = 169), infections (n = 51), other inflammatory diseases (n = 126), and acute lymphoblastic leukemia (ALL, n = 147). In addition, samples from 23 healthy controls were included.Results: The sCAL turbo assay correlated well with the MRP8/14 ELISA used in previous validation studies (r = 0.99, p < 0.001). It could reliably differentiate SJIA from all other diagnoses with significant accuracy (cutoff at 10,500 ng/ml, sensitivity 84%, specificity 94%, ROC area under curve 0.960, p < 0.001).Conclusions: Serum calprotectin analyses are a helpful tool supporting the diagnosis of SJIA in children with prolonged fever or inflammatory disease. Here, we show that an immuno-turbidimetric assay for detection of serum calprotectin on an automated laboratory instrument can be implemented in clinical laboratory settings to facilitate its use as a diagnostic routine test in clinical practice.
40.	Glerup, Mia, et al. (författare) Changing patterns in treatment, remission status and categories in a long-term Nordic cohort study of juvenile idiopathic arthritis. 2022 Ingår i: Arthritis care & research. - : Wiley. - 2151-4658 .- 2151-464X. Tidskriftsartikel (refereegranskat)abstract To explore sustainability of achieved remission off medication and defined ILAR categories in juvenile idiopathic arthritis (JIA). To describe the trajectory of disease course over time by comparing treatment, disease activity and ILAR categories from baseline, 8 and 18years of disease.Included were 373 of the 510 initially recruited consecutive cases of JIA from the prospective longitudinal, population-based Nordic JIA cohort with disease onset during 1997-2000 from Denmark, Norway, Sweden, and Finland in an 18-year follow-up study. Clinical data was collected consecutively at baseline, 8 and 18years of disease, and evaluated regarding treatment, disease activity and ILAR category.Significantly more patients (70%) were off medication after 18years of follow-up compared to after 8years (59.7%); nevertheless, the number of patients in remission had not increased (52% versus 51%). Twelve percent of patients changed ILAR category between 8 and 18years after disease onset. Almost half of the changes were due to updated information about heredity in a first degree relative. In the same period, the psoriatic group increased significantly in number (p<0.001) contrasting the oligoarticular category, which decreased (p=0.02). The undifferentiated group increased 24% from 8 to 18years, however, this was not significant (p=0.06).In this Nordic JIA cohort study the remission rate did not increase even though significantly more patients were off medication at the 18-year follow-up compared to 8years after disease onset. The distribution of patients in the ILAR categories continued to change significantly throughout the 18-year study period.
41.	Glerup, Mia, et al. (författare) Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis : a longitudinal study of the Nordic JIA cohort 2019 Ingår i: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 17:1 Tidskriftsartikel (refereegranskat)abstract BackgroundTo determine the serum levels of the lectin pathway proteins early in the disease course and 17 years after disease onset and to correlate the protein levels to markers of disease activity in participants from a population-based Nordic juvenile idiopathic arthritis (JIA) cohort. Additionally, to assess the predictive value of lectin pathway proteins with respect to remission status.MethodsA population-based cohort study of consecutive cases of JIA with a disease onset from 1997 to 2000 from defined geographical areas of Finland, Sweden, Norway and Denmark with 17 years of follow-up was performed. Clinical characteristics were registered and H-ficolin, M-ficolin, MASP-1, MASP-3, MBL and CL-K1 levels in serum were analyzed.ResultsIn total, 293 patients with JIA were included (mean age 23.7 ± 4.4 years; mean follow-up 17.2 ± 1.7 years). Concentrations of the lectin protein levels in serum were higher at baseline compared to the levels 17 years after disease onset (p ≤ 0.006, n = 164). At baseline, the highest level of M-ficolin was observed in systemic JIA. Further, high M-ficolin levels at baseline and at 17-year follow-up were correlated to high levels of ESR. In contrast, high MASP-1 and MASP-3 tended to correlate to low ESR. CL-K1 showed a negative correlation to JADAS71 at baseline.None of the protein levels had prognostic abilities for remission status 17 years after disease onset.ConclusionWe hypothesize that increased serum M-ficolin levels are associated with higher disease activity in JIA and further, the results indicate that MASP-1, MASP-3 and CL-K1 are markers of inflammation.
42.	Glerup, Mia, et al. (författare) Long-Term Outcome of Temporomandibular Joint Arthritis in Juvenile Idiopathic Arthritis : Results of 18-Year Follow-up in the Population-Based Nordic JIA Cohort 2018 Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
43.	Glerup, Mia, et al. (författare) Long-Term Outcomes in Juvenile Idiopathic Arthritis : Eighteen Years of Follow-Up in the Population-Based Nordic Juvenile Idiopathic Arthritis Cohort 2020 Ingår i: Arthritis care & research. - : WILEY. - 2151-464X .- 2151-4658. ; 72:4, s. 507-516 Tidskriftsartikel (refereegranskat)abstract Objective: The present study was undertaken to assess the long-term course, remission rate, and disease burden in juvenile idiopathic arthritis (JIA) 18 years after disease onset in a population-based setting from the early biologic era.Methods: A total of 510 consecutive cases of JIA with disease onset between 1997 and 2000 from defined geographic regions in Denmark, Norway, Sweden, and Finland were prospectively included in this 18-year cohort study. At the follow-up visit, patient-reported demographic and clinical data were collected.Results: The study included 434 (85%) of the 510 eligible JIA participants. The mean +/- SD age was 24.0 +/- 4.4 years. The median juvenile arthritis disease activity score in 71 joints (JADAS-71) was 1.5 (interquartile range [IQR] 0-5), with the enthesitis-related arthritis (ERA) category of JIA having the highest median score (4.5 [IQR 1.5-8.5], P = 0.003). In this cohort, 46% of patients still had active disease, and 66 (15%) were treated with synthetic disease-modifying antirheumatic drugs and 84 (19%) with biologics. Inactive disease indicated by a JADAS-71 score of <1 was seen in 48% of participants. Clinical remission off medication (CR) was documented in 33% of the participants with high variability among the JIA categories. CR was most often seen in persistent oligoarticular and systemic arthritis and least often in ERA (P < 0.001).Conclusion: A substantial proportion of the JIA cohort did not achieve CR despite new treatment options during the study period. The ERA category showed the worst outcomes, and in general there is still a high burden of disease in adulthood for JIA.
44.	Glerup, Mia, et al. (författare) Long-term outcomes in juvenile idiopathic arthritis: 18 years of follow-up in the population-based Nordic Juvenile Idiopathic Arthritis (JIA) cohort. 2020 Ingår i: Arthritis care & research. - : Wiley. - 2151-4658 .- 2151-464X. ; 72:4, s. 507-516 Tidskriftsartikel (refereegranskat)abstract This study assessed the long-term course, remission rate and disease burden in juvenile idiopathic arthritis (JIA) 18 years after disease onset in a population-based setting from the early biologic era.A total of 510 consecutive cases of JIA with disease onset between 1997 and 2000 from defined geographic regions in Denmark, Norway, Sweden and Finland were prospectively included in this 18-year cohort study. At the follow-up visit, patient-reported, demographic and clinical data were collected.The study included 434 (85%) of the 510 eligible JIA participants. The mean age ± SD was 24.0 ± 4.4 years. The median juvenile arthritis disease activity (JADAS71) score was 1.5 (IQR 0-5), with the ERA category of JIA having the highest median score, 4.5 (IQR 1.5-8.5) (P=0.003). In this cohort, 46% still had active disease, and 66 (15%) were treated with synthetic disease-modifying anti-rheumatic drugs and 84 (19%) with biologics. Inactive disease indicated by JADAS71 <1 was seen in 48% of participants. Clinical remission off medication (CR) was documented in 33% of the participants with high variability among the JIA categories. CR was most often seen in persistent oligoarticular and systemic arthritis and least often in ERA (P<0.001).A high prevalence of the JIA cohort did not achieve CR despite new treatment options during the study period. The ERA category showed the worst outcomes and, in general, there is still a high burden of disease in adulthood for JIA. This article is protected by copyright. All rights reserved.
45.	Glerup, Mia, et al. (författare) Long-term Outcomes of Temporomandibular Joints in Juvenile Idiopathic Arthritis. 2020 Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 47:4 Tidskriftsartikel (refereegranskat)abstract To determine the prevalence of orofacial symptoms, dysfunctions, and deformities of the temporomandibular joint (TMJ) in juvenile idiopathic arthritis (JIA) 17 years after disease onset.Drawn from a prospective, population-based Nordic JIA cohort with disease onset from 1997-2000, 420 consecutive cases were eligible for orofacial evaluation of TMJ involvement. The follow-up visit included demographic data, a standardized clinical orofacial examination, and fullface cone-beam computed tomography (CBCT). For comparison, 200 age-matched healthy controls were used.Of 420 eligible participants with JIA, 265 (63%) were included (mean age 23.5 ± 4.2 years) and completed a standardized clinical orofacial examination. Of these, 245 had a full-face CBCT performed. At least one orofacial symptom was reported by 33%. Compared to controls, the JIA group significantly more often reported TMJ pain, TMJ morning stiffness, and limitation on chewing. Furthermore, among participants reporting complaints, the number of symptoms was also higher in the JIA. The mean maximal incisal opening was lower in the JIA group (p<0.001), and TMJ pain on palpation was more frequent. Condylar deformities and/or erosions were observed in 61% as assessed by CBCT, showing bilateral changes in about 70%. Risk factors of condylar deformities were orofacial dysfunction or biologic treatment; enthesitis-related arthritis was protective.This first study on long-term consequences of TMJ involvement in a population-based JIA cohort reports persistence of comprehensive symptoms, dysfunctions, and damage of the TMJ into adulthood. We suggest interdisciplinary follow-up of JIA patients also in adulthood.
46.	Glerup, Mia, et al. (författare) Longterm Outcomes of Temporomandibular Joints in Juvenile Idiopathic Arthritis : 17 Years of Followup of a Nordic Juvenile Idiopathic Arthritis Cohort 2020 Ingår i: Journal of Rheumatology. - : J RHEUMATOL PUBL CO. - 0315-162X .- 1499-2752. ; 47:5, s. 730-738 Tidskriftsartikel (refereegranskat)abstract Objective: To determine the prevalence of orofacial symptoms, dysfunctions, and deformities of the temporomandibular joint (TMJ) in juvenile idiopathic arthritis (JIA) 17 years after disease onset.Methods: Drawn from a prospective, population-based Nordic JIA cohort with disease onset from 1997 to 2000, 420 consecutive cases were eligible for orofacial evaluation of TMJ involvement. The followup visit included demographic data, a standardized clinical orofacial examination, and full-face cone-beam computed tomography (CBCT). For comparison, 200 age-matched healthy controls were used.Results: Of 420 eligible participants with JIA, 265 (63%) were included (mean age 23.5 +/- 4.2 yrs) and completed a standardized clinical orofacial examination. Of these, 245 had a full-face CBCT performed. At least 1 orofacial symptom was reported by 33%. Compared to controls, the JIA group significantly more often reported TMJ pain, TMJ morning stiffness, and limitation on chewing. Further, among participants reporting complaints, the number of symptoms was also higher in JIA. The mean maximal incisal opening was lower in the JIA group (p < 0.001), and TMJ pain on palpation was more frequent. Condylar deformities and/or erosions were observed in 61% as assessed by CBCT, showing bilateral changes in about 70%. Risk factors of condylar deformities were orofacial dysfunction or biologic treatment; enthesitis-related arthritis was protective.Conclusion: This study of the longterm consequences of TMJ involvement in a population-based JIA cohort reports persistence of comprehensive symptoms, dysfunctions, and damage of the TMJ into adulthood. We suggest interdisciplinary followup of JIA patients also in adulthood.
47.	Glerup, Mia, et al. (författare) Remission Status after 18 Years of Follow-up in the Population-Based Nordic Juvenile Idiopathic Arthritis (JIA) Cohort 2018 Ingår i: Arthritis & Rheumatology. - : John Wiley & Sons. - 2326-5191 .- 2326-5205. ; 70 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
48.	Hagström, Naima, et al. (författare) A qualitative evaluation of the specific carbohydrate diet for juvenile idiopathic arthritis based on children's and parents' experiences 2023 Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 21:1 Tidskriftsartikel (refereegranskat)abstract BackgroundInsights into the immunological role of the gastrointestinal tract in autoimmune conditions have led to the investigation of diet as a potential adjunctive treatment option for juvenile idiopathic arthritis (JIA). The specific carbohydrate diet (SCD) has shown promising results. However, studies on participants’ experiences of dietary interventions in JIA are rare. In this study we investigated the experiences of children and parents’ who had participated in a four-week intervention with SCD aiming to examine the potential anti-inflammatory effects.ObjectivesTo conduct a qualitative evaluation exploring children’s and parents’ experiences of the dietary intervention, how they navigated challenges, and their support requirements.MethodsSemi-structured interviews were conducted with 12 children and 15 parents from 13 families, who were interviewed individually and together. The transcripts were analysed using systematic text condensation.ResultsMost participants interviewed found the intervention beneficial, with 12 out of 13 reporting positive effects, such as reduced pain and morning stiffness, and improved gastrointestinal function. Many participants reported being willing to repeat the intervention in the current form. Despite facing challenges, all children followed the diet for one to three months, with some continuing to follow a modified version. Facing the socio-emotional consequences of adhering to the diet was challenging for children. These were handled by focusing on the positive aspects and by relying on the supportive environment available. Parents struggled with practical issues since the diet required hard work, time, and money. Areas identified as requiring additional support include finding simple, quick, and child-friendly solutions, strengthening organizational food skills such as meal planning, and preparation prior to starting the intervention regarding socio-emotional aspects.ConclusionNavigating the dietary treatment was considered challenging, practically for the parents and socio-emotionally for the children. Based on the reported challenges and participants’ suggestions the intervention could be optimised by providing support and solutions in relation to the practical issues and better preparation regarding dealing with the socio-emotional consequences. Despite the difficulties, the participants reported overall positive experiences of, and attitudes towards, the current setup. Consequently, dietary interventions, such as the SCD, may be regarded as suitable targets for further research.
49.	Kahn, Robin, et al. (författare) Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms 2022 Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62 Tidskriftsartikel (refereegranskat)abstract Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
50.	Kazamia, Kalliopi, et al. (författare) Children with juvenile idiopathic arthritis frequently experience interruptions to their medical therapy 2014 Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 103:5, s. 529-536 Tidskriftsartikel (refereegranskat)abstract AimTo study real-life experiences of drug treatment discontinuations and safety in a well-defined cohort of patients with juvenile idiopathic arthritis (JIA), over an eleven-year period in Uppsala County, Sweden. MethodsClinical charts of all incident and prevalent cases of juvenile arthritis were reviewed prospectively by an experienced paediatric rheumatologist. Each patient file was supplemented retrospectively regarding hereditary diseases, clinical data and aspects of pharmacological treatment. ResultsSevere adverse events from methotrexate or biological agents were rare, but 84 occasions of interrupted therapy due to adverse events or inefficacy were identified within 225 treatment periods (37.3%) in the 156 patients (108 girls and 48 boys) studied. The median observation period was 8.6years after disease onset (minimum 1.33, maximum 17.5years). Oral and subcutaneous methotrexate caused adverse events in 22.6% of the treatment periods and biological agents in 19.2% (p=0.71). Discontinuation of treatment periods was equally common for methotrexate (38.7%) and biological agents (33.3%) (p=0.53). ConclusionOur study shows a high percentage of interrupted medical therapies, due to adverse events or inefficacy, in children with JIA. Adverse events from methotrexate and biological agents were seldom severe. The results highlight the need for better predictive factors to guide therapy.

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