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1.	Laurell, Louise, 1959, et al. (author) Comparison of ultrasonography with Doppler and MRI for assessment of disease activity in juvenile idiopathic arthritis: a pilot study. 2012 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 10:1 Journal article (peer-reviewed)abstract ABSTRACT: BACKGROUND: In juvenile idiopathic arthritis (JIA), the trend towards early therapeutic intervention and the development of new highly effective treatments have increased the need for sensitive and specific imaging. Numerous studies have demonstrated the important role of MRI and US in adult rheumatology. However, investigations of imaging in JIA are rare, and no previous study has been comparing MRI with Doppler ultrasonography (US) for assessment of arthritis. The aim of the present study was to compare the two imaging methods regarding their usefulness for evaluating disease activity in JIA, and to compare the results with those obtained in healthy controls. METHODS: In 10 JIA patients (median age 14 years, range 11--18), 11 joints (six wrists, three knees, two ankles) with arthritis were assessed by color Doppler US and MRI. The same imaging modalities were used to evaluate eight joints (three wrists, three knees, two ankles) in six healthy age- and sex-matched controls. The US examinations of both the patients and controls were compared with the MRI findings. RESULTS: In 10 JIA patients, US detected synovial hypertrophy in 22 areas of 11 joints, 86% of which had synovial hyperemia, and MRI revealed synovitis in 36 areas of the same 11 joints. Erosions were identified by US in two areas of two joints and by MRI in six areas of four joints. Effusion was shown by US in nine areas of six joints and by MRI in 17 areas of five joints. MRI detected juxta-articular bone marrow edema in 16 areas of eight joints. CONCLUSIONS: The results of this pilot study indicate that both MRI and US provide valuable imaging information on disease activity in JIA. Importantly, the two techniques seem to complement each other and give partly different information. Although MRI is considered to be the reference standard for advanced imaging in adult rheumatology, US seems to provide useful imaging information that could make it an option in daily clinical practice, in JIA as well as in adult rheumatology. However, the current work represents a pilot study, and thus our results need to be confirmed in a larger prospective clinical investigation.
2.	Laurell, Louise, 1959, et al. (author) Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the ankle region. A descriptive interventional study. 2011 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 9:1 Journal article (peer-reviewed)abstract ABSTRACT:BACKGROUND: The ankle region is frequently involved in juvenile idiopathic arthritis (JIA) but difficult to examine clinically due to its anatomical complexity. The aim of the study was to evaluate the role of ultrasonography (US) of the ankle and midfoot (ankle region) in JIA. Doppler-US detected synovial hypertrophy, effusion and hyperemia and US was used for guidance of steroid injection and to assess treatment efficacy. METHODS: Forty swollen ankles regions were studied in 30 patients (median age 6.5 years, range 1-16 years) with JIA. All patients were assessed clinically, by US (synovial hypertrophy, effusion) and by color Doppler (synovial hyperemia) before and 4 weeks after US-guided steroid injection. RESULTS: US detected 121 compartments with active disease (joints, tendon sheaths and 1 ganglion cyst). Multiple compartments were involved in 80% of the ankle regions. The talo-crural joint, posterior subtalar joint, midfoot joints and tendon sheaths were affected in 78%, 65%, 30% and 55% respectively. Fifty active tendon sheaths were detected, and multiple tendons were involved in 12 of the ankles. US-guidance allowed accurate placement of the corticosteroid in all 85 injected compartments, with a low rate of subcutaneous atrophy (4,7%). Normalization or regression of synovial hypertrophy was obtained in 89%, and normalization of synovial hyperemia in 89%. Clinical resolution of active arthritis was noted in 72% of the ankles. CONCLUSIONS: US enabled exact anatomical location of synovial inflammation in the ankle region of JIA patients. The talo-crural joint was not always involved. Disease was frequently found in compartments difficult to evaluate clinically. US enabled exact guidance of steroid injections, gave a low rate of subcutaneous atrophy and was proved valuable for follow-up examinations. Normalization or regression of synovial hypertrophy and hyperemia was achieved in most cases, which supports the notion that US is an important tool in the management of ankle involvement in JIA.
3.	Laurell, Louise, et al. (author) Ultrasonography and color Doppler in juvenile idiopathic arthritis: diagnosis and follow-up of ultrasound-guided steroid injection in the wrist region. A descriptive interventional study 2012 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 10 Journal article (peer-reviewed)abstract Background: The wrist region is one of the most complex joints of the human body. It is prone to deformity and functional impairment in juvenile idiopathic arthritis (JIA), and is difficult to examine clinically. The aim of this study was to evaluate the role of ultrasonography (US) with Doppler in diagnosis of synovitis, guidance of steroid injections, and follow-up examinations of the wrist in JIA. Methods: In 11 patients (median age 12.5 years, range 2-16), 15 wrists with clinically active arthritis were assessed clinically by US and color Doppler (Logiq 9, GE, 16-4 MHz linear transducer) prior to and 1 and 4 weeks after US-guided steroid injection. Results: US detected synovitis in the radio-carpal joints, the midcarpal joints, and the tendon sheaths in 87%, 53% and 33% of the wrists, respectively. Multiple compartments were involved in 67%. US-guidance allowed accurate placement of steroid in all 21 injected compartments, with a low rate of subcutaneous atrophy. Synovial hypertrophy was normalized in 86% of the wrists, hyperemia in 91%, and clinically active arthritis in 80%. Conclusions: US enabled detection of synovial inflammation in compartments that are difficult to evaluate clinically and exact guidance of injections, and it was valuable for follow-up examinations. Normalization of synovitis was achieved in most cases, which supports the notion that US is an important tool in management of wrist involvement in JIA.
4.	Laurell, Louise, et al. (author) Ultrasonography and color Doppler of proximal gluteal enthesitis in juvenile idiopathic arthritis: a descriptive study. 2011 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 9:1 Journal article (peer-reviewed)abstract ABSTRACT: Background The presence of enthesitis (insertional inflammation) in patients with juvenile idiopathic arthritis (JIA) is difficult to establish clinically and may influence classification and treatment of the disease. We used ultrasonography (US) and color Doppler (CD) imaging to detect enthesitis at the small and deep-seated proximal insertion of the gluteus medius fascia on the posterior iliac crest where clinical diagnosis is difficult. The findings in JIA patients were compared with those obtained in healthy controls and with the patients' MRI results. Methods Seventy-six proximal gluteus medius insertions were studied clinically (tenderness to palpation of the posterior iliac crest) and by US and CD (echogenicity, thickness, hyperemia) in 38 patients with JIA and in 38 healthy controls, respectively (median age 13 years, range 7-18 years). In addition, an additional MRI examination of the sacroiliac joints and iliac crests was performed in all patients. Results In patients with focal, palpable tenderness, US detected decreased echogenicity of the entheses in 53% of the iliac crests (bilateral in 37% and unilateral in 32%). US also revealed significantly thicker entheses in JIA patients compared to healthy controls (p < 0.003 left side, p < 0.001 right side). There was no significant difference in thickness between the left and right sides in individual subjects. Hyperemia was detected by CD in 37% (28/76) of the iliac crests and by contrast-enhanced MRI in 12% (6/50). Conclusions According to US, the gluteus medius insertion was thicker in JIA patients than in controls, and it was hypoechoic (enthesitis) in about half of the patients. These findings may represent chronic, inactive disease in some of the patients, because there was only limited Doppler flow and MRI contrast enhancement. The present study indicates that US can be useful as an adjunct to clinical examination for improved assessment of enthesitis in JIA. This may influence disease classification, ambition to treat, and choice of treatment regimen.
5.	Berntson, Lillemor, et al. (author) 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 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12, s. 22- Journal article (peer-reviewed)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.
6.	Bohm, Marek, et al. (author) Clinical features of childhood granulomatosis with polyangiitis (wegener's granulomatosis) 2014 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12:18 Journal article (peer-reviewed)abstract Abstract Background Granulomatosis with polyangiitis (GPA), formerly known as Wegener’s granulomatosis (WG), belongs to the group of ANCA-associated necrotizing vasculitides. This study describes the clinical picture of the disease in a large cohort of GPA paediatric patients.Children with age at diagnosis ≤ 18 years, fulfilling the EULAR/PRINTO/PRES GPA/WG classification criteria were extracted from the PRINTO vasculitis database. The clinical signs/symptoms and laboratory features were analysed before or at the time of diagnosis and at least 3 months thereafter and compared with other paediatric and adult case series (>50 patients) derived from the literature. Findings The 56 children with GPA/WG were predominantly females (68%) and Caucasians (82%) with a median age at disease onset of 11.7 years, and a median delay in diagnosis of 4.2 months. The most frequent organ systems involved before/at the time of diagnosis were ears, nose, throat (91%), constitutional (malaise, fever, weight loss) (89%), respiratory (79%), mucosa and skin (64%), musculoskeletal (59%), and eye (35%), 67% were ANCA-PR3 positive, while haematuria/proteinuria was present in > 50% of the children. In adult series, the frequency of female involvement ranged from 29% to 50% with lower frequencies of constitutional (fever, weight loss), ears, nose, throat (oral/nasal ulceration, otitis/aural discharge), respiratory (tracheal/endobronchial stenosis/obstruction), laboratory involvement and higher frequency of conductive hearing loss than in this paediatric series. Conclusions Paediatric patients compared to adults with GPA/WG have similar pattern of clinical manifestations but different frequencies of organ involvement.
7.	Cedströmer, Anna-Lena, 1974, et al. (author) Temporomandibular condylar alterations in juvenile idiopathic arthritis most common in longitudinally severe disease despite medical treatment 2014 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 12 Journal article (peer-reviewed)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.
8.	Cedströmer, Anna-Lena, 1974, et al. (author) Temporomandibular signs, symptoms, joint alterations and disease activity in juvenile idiopathic arthritis – an observational study 2013 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 11:37 Journal article (peer-reviewed)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.
9.	Lundberg, Veronica, et al. (author) Health-related quality of life in girls and boys with juvenile idiopathic arthritis : self- and parental reports in a cross-sectional study 2012 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 10 Journal article (peer-reviewed)abstract Background: Juvenile Idiopathic Arthritis (JIA) affects children and adolescents with both short-term and long-term disability. These children also report lower health-related quality of life (HRQOL) compared to their healthy peers. However, there seems to be some discrepancies between self- and parent-reports, and gender differences need to be further studied. This study aims to describe HRQOL in girls and boys with JIA, and to explore gender differences in self-reports compared to parent-reports of HRQOL in children with JIA.Methods: Fifty-three children and adolescents with JIA (70% girls and 30% boys) with a median age of 14 years (8–18 years), and their parents, participated in this cross-sectional study in Sweden. Data was systematically collected prior to ordinary visits at a Pediatric outpatient clinic, during a period of 16 months (2009–2010). Disability was assessed with the Childhood Health Assessment Questionnaire (CHAQ), and disease activity by physicians’ assessments and Erythrocyte Sedimentation Rate (ESR). The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) was used to assess self- and parent-reports of HRQOL in the child.Results: In this sample of children with generally low disease activity and mild to moderate disability, more than half of the children experienced suboptimal HRQOL, equally in girls and boys. Significant differences between self- and parent-reports of child HRQOL were most evident among girls, with lower parent-reports regarding the girl’s physical- and psychosocial health as well as in the total HRQOL score. Except for the social functioning subscale, where parents’ reports were higher compared to their sons, there were no significant differences between boys- and parent-reports.Conclusions: More than half of the girls and boys experienced suboptimal HRQOL in this sample, with no gender differences. However, there were differences between self- and parent-reports of child HRQOL, with most significant differences found among the girls. Thus, differences between self- and parent-reports of child HRQOL must be taken into account in clinical settings, especially among girls with JIA.
10.	Sandstedt, Eva, 1952, et al. (author) Muscle strength, physical fitness and well-being in children and adolescents with juvenile idiopathic arthritis and the effect of an exercise programme: a randomized controlled trial. 2013 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 11:1 Journal article (peer-reviewed)abstract Decreased muscle strength, fitness and well-being are common in children and adolescents with juvenile idiopathic arthritis (JIA) compared to healthy peers. Biological drugs have improved health in children with JIA, but despite this pain is still a major symptom and bone health is reported as decreased in the group. The improvement made by the biological drugs makes it possible to more demanding exercises. To jump is an exercise that can improve bone heath, fitness and muscle strength. The aim of the study was to see if an exercise programme with jumps had an effect on muscle strength, physical fitness and well-being and how it was tolerated.
11.	Visvanathan, Sudha, et al. (author) The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial. 2010 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 8:1 Journal article (peer-reviewed)abstract ABSTRACT: BACKGROUND: We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA). METHODS: In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP). RESULTS: At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders. CONCLUSION: Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders. TRIAL REGISTRATION: NCT00036374.
12.	Arnstad, Ellen Dalen, et al. (author) Fatigue in young adults with juvenile idiopathic arthritis 18 years after disease onset : data from the prospective Nordic JIA cohort 2021 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Journal article (peer-reviewed)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.
13.	Arvonen, Miika, et al. (author) Gut microbiota-host interactions and juvenile idiopathic arthritis 2016 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 14 Research review (peer-reviewed)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.
14.	Backlund, Malin, et al. (author) A cross-sectional cohort study of the activity and turnover of neutrophil granulocytes in juvenile idiopathic arthritis 2021 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Journal article (peer-reviewed)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.
15.	Berntson, Lillemor, 1957- (author) A pilot study of possible anti-inflammatory effects of the specific carbohydrate diet in children with juvenile idiopathic arthritis 2021 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Journal article (peer-reviewed)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.
16.	Berntson, Lillemor, 1957-, et al. (author) Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis : a cross-sectional study 2024 In: Pediatric Rheumatology. - : Springer Nature. - 1546-0096. ; 22:1 Journal article (peer-reviewed)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.
17.	Berntson, Lillemor, 1957-, et al. (author) Haptoglobin in Juvenile Idiopathic Arthritis 2022 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20:1 Journal article (peer-reviewed)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.
18.	Berntson, L, et al. (author) PReS-FINAL-2071: Anti-type II collagen antibodies, anti-CCP, IgA-RF and IgM-RF are associated with joint damage eight years after onset of juvenile idiopathic arthritis (JIA) 2013 In: Pediatric Rheumatology. - 1546-0096. ; 11:Suppl. 2 Journal article (peer-reviewed)
19.	Berntson, Lillemor, 1957-, et al. (author) Severe Raynaud's phenomenon from ethosuximide raised concern over possible onset of systemic vasculitis : a case report 2022 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 20 Journal article (peer-reviewed)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.
20.	Berthold, Elisabet, et al. (author) The risk of depression and anxiety is not increased in individuals with juvenile idiopathic arthritis - results from the south-Swedish juvenile idiopathic arthritis cohort 2022 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20:1, s. 1-9 Journal article (peer-reviewed)abstract BackgroundChildren with chronic diseases are reported to have increased risk of psychiatric comorbidity. Few studies have investigated this risk in juvenile idiopathic arthritis (JIA), with conflicting results. We performed a population-based, longitudinal cohort study of the risk of depression and anxiety in south-Swedish patients with juvenile arthritis.MethodsThe south-Swedish JIA cohort (n = 640), a population-based cohort with validated JIA diagnosis 1980 – 2010 and comparators, a reference group of 3200 individuals free from JIA, matched for sex, year of birth and residential region, was used. Data on comorbid diagnosis with depression or anxiety were obtained from the Skåne Healthcare Register, containing all healthcare contacts in the region, from 1998 to 2019. We used Cox proportional models for the calculation of hazard ratios.ResultsDuring the study period, 1998 to 2019, 93 (14.5%) of the individuals in the JIA group were diagnosed with depression, and 111 (17.3%) with anxiety. Corresponding numbers among the references was 474 (14.8%) with depression and 557 (17.4%) with anxiety. Hazard ratio for depression was 1.1 (95% CI 0.9 – 1.5) in females and 0.8 (95% CI 0.5 – 1.4) in males, and for anxiety 1.2 (95% CI 0.9 – 1.5) in females and 0.6 (95% CI 0.4 – 1.1) in males. There were no statistically significant hazard ratios when analyzing subgroups of JIA patients with long disease duration or treatment with disease-modifying antirheumatic drugs.ConclusionsIndividuals with JIA do not have any statistically increased risk of being diagnosed with depression or anxiety compared to matched references.
21.	Beukelman, Timothy, et al. (author) A survey of national and multi-national registries and cohort studies in juvenile idiopathic arthritis : challenges and opportunities 2017 In: Pediatric Rheumatology. - : BIOMED CENTRAL LTD. - 1546-0096. ; 15 Journal article (peer-reviewed)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.	Carlsson, Alexandra Dimitrijevic, et al. (author) Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations 2019 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 17:1 Journal article (peer-reviewed)abstract Background The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). Methods Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophizing, pain locations and jaw function). Results JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. Conclusions Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.
23.	Dimitrijevic Carlsson, Alexandra, 1966-, et al. (author) Increase in stress contributes to impaired jaw function in juvenile idiopathic arthritis : a two-year prospective study 2024 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 22:1 Journal article (peer-reviewed)abstract BackgroundStress in patients with Juvenile Idiopathic Arthritis (JIA) has been found to be associated with orofacial pain, psychological distress, jaw dysfunction and loss of daily activities in a cross-sectional study. The aim of this study was to investigate the relations between stress and change of stress over time versus changes in orofacial pain, psychosocial factors and jaw function over a two-year period in patients with JIA.MethodsThis is a two-year prospective follow-up study involving 40 JIA patients. At baseline (2015) the median age was 12 years and at two-year follow up (2018) 14 years. The JIA patients were examined clinically and with questionnaires at baseline and follow-up with the diagnostic criteria for temporomandibular disorders (DC/TMD) and completed the same set of DC/TMD questionnaires regarding orofacial pain symptoms and psychosocial factors.ResultsChange in stress was associated with change in catastrophizing, psychological distress as well as limitation in general function and jaw function.ConclusionsThis study emphasizes the importance of maintaining a low stress level in patients with JIA since an increase in stress level over a two-year period seems to impair jaw function as well as psychological distress and catastrophizing.
24.	Ekelund, Maria, et al. (author) Psoriasis and associated variables in classification and outcome of juvenile idiopathic arthritis - an eight-year follow-up study 2017 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 15 Journal article (peer-reviewed)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.
25.	Floden, A, et al. (author) A qualitative study examining the validity and comprehensibility of physical activity items: developed and tested in children with juvenile idiopathic arthritis 2019 In: Pediatric rheumatology online journal. - : Springer Science and Business Media LLC. - 1546-0096. ; 17:1, s. 16- Journal article (peer-reviewed)
26.	Glerup, Mia, et al. (author) Complement lectin pathway protein levels reflect disease activity in juvenile idiopathic arthritis : a longitudinal study of the Nordic JIA cohort 2019 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 17:1 Journal article (peer-reviewed)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.
27.	Hagström, Naima, et al. (author) A qualitative evaluation of the specific carbohydrate diet for juvenile idiopathic arthritis based on children's and parents' experiences 2023 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 21:1 Journal article (peer-reviewed)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.
28.	Hjelmgren, H, et al. (author) Multi-inflammatory syndrome in children (MIS-C) associated with COVID-19: a nursing perspective experience report from a high-income tertiary paediatric hospital context 2023 In: Pediatric rheumatology online journal. - 1546-0096. ; 21:1, s. 5- Journal article (peer-reviewed)
29.	Kindgren, Erik, et al. (author) Early feeding and risk of Juvenile idiopathic arthritis: a case control study in a prospective birth cohort 2017 In: Pediatric Rheumatology. - : BIOMED CENTRAL LTD. - 1546-0096. ; 15 Journal article (peer-reviewed)abstract Background: Juvenile idiopathic arthritis (JIA) is considered to be an autoimmune disease, but the etiology is unknown. We decided to study the influence of early nutrition on later development of JIA. Methods: All parents with children born between October 1, 1997 and October 1, 1999 in Southeast Sweden were asked to participate in the ABIS prospective cohort study (All Babies in Southeast Sweden), At 1 year, questionnaires with information on breastfeeding and introduction of foods were completed by 10,565 families. We identified 32 children with JIA and 111 children with non-chronic arthritis with completed questionnaires after delivery and after 1 year. A multivariable logistic regression model, adjusted for relevant factors, was performed to calculate the association between JIA and feeding during the first year of life. Results: An increased risk for JIA was found in children who had breast fed for less than 4 months, as opposed to those who were continued on breast milk beyond 4 months of age (aOR 3.5, 95% CI 1.4-8,5; p = 0.006). A short duration of exclusive as well as total breastfeeding was associated with an increased risk of JIA (aOR 1.3, 95% CI 1.1-1.6; p = 0.008 and aOR 1.2, 95% CI 1.1-1.3; p amp;lt; 0.001). All associations between breastfeeding and JIA persisted after adjustment. There was no relationship between early nutrition and non-chronic arthritis. Conclusions: Our results indicate that there are different disease mechanisms for different types of arthritis in childhood. Longer duration of breastfeeding (both total and exclusive) may protect against development of JIA. Mothers should be encouraged to breast-feed their babies exclusively, if at all possible, for 4 months and continue partial breastfeeding for an extended time when foreign proteins are introduced.
30.	Kindgren, Erik, et al. (author) Heavy metals in fish and its association with autoimmunity in the development of juvenile idiopathic arthritis: a prospective birth cohort study 2019 In: Pediatric Rheumatology. - : BMC. - 1546-0096. ; 17 Journal article (peer-reviewed)abstract BackgroundThe etiology of Juvenile Idiopathic Arthritis (JIA) is poorly understood. The purpose of this study was to examine the possible influence of early nutrition on later development of JIA.MethodsIn a population-based prospective birth cohort of 15,740 children we collected nutritional data, including fish consumption, and biological samples during pregnancy, at birth and at different ages. 16years after study inclusion we identified 42 children with JIA, of whom 11 were positive for Antinuclear Antibodies (ANA). Heavy metals were analysed in cord blood of all 42 JIA patients and 40 age and sex-matched controls. A multivariable logistic regression model, adjusted for relevant factors, was used as well as Mann-Whitney U-test.ResultsFish consumption more than once a week during pregnancy as well as during the childs first year of life was associated with an increased risk of JIA (aOR 4.5 (1.95-10.4); pamp;lt;0.001 and aOR 5.1 (2.1-12.4) pamp;lt;0.001) and of ANA-positivity (aOR 2.2 (1.4-3.6); p=0.002 and pamp;lt;0.001). Concentrations of Al, Cd, Hg and Li in cord blood were significantly higher in the JIA-group than in controls. The ANA-positive, all of whom had consumed fish amp;gt;once/week their first year, had significantly higher concentrations of Al (pamp;lt;0.001), Cd (p=0.003), and Li (pamp;lt;0.001) in cord blood than controls. Frequency of fish consumption correlated with concentrations of Cd (p=0.003), Li (p=0.015) and Hg (p=0.011).ConclusionsModerate exposure to heavy metals, associated with fish consumption, during pregnancy and early childhood may cause effects on the immune system of the offspring, resulting in ANA positivity and JIA.
31.	Kindgren, Erik, et al. (author) Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis : a prospective cohort study 2021 In: Pediatric Rheumatology. - : BMC. - 1546-0096. ; 19:1 Journal article (peer-reviewed)abstract Background The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA. Methods In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors. Results Exposure to antibiotics during the periods 1-12 months, 1-3 years and 5-8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11-9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36-3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15-2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment. The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA. Conclusions Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.
32.	Lewander, Per, et al. (author) Serum levels of soluble urokinase plasminogen activator receptor in juvenile idiopathic arthritis: a single-center Swedish case-control study 2023 In: Pediatric Rheumatology. - : BMC. - 1546-0096. ; 21:1 Journal article (peer-reviewed)abstract ObjectivesReliable biomarkers in the early stages of idiopathic arthritis (JIA) are scarce and the disease heterogeneity makes it clinically challenging to predict the risk of joint damage. Biomarkers with prognostic potential are warranted in order to individualize treatment and follow-up in JIA. The soluble urokinase plasminogen activator receptor (suPAR) has been reported as an easily measurable biomarker for prognosis and severity in several rheumatic diseases but it has never been studied in JIA.MethodsSera from 51 well-characterized patients with JIA and 50 age- and sex-matched control subjects were collected and stored for later analysis of suPAR. Patients were carefully followed clinically over 3 years and analysis of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (anti-CCP) were analyzed as part of clinical routine. Signs of joint erosions were evaluated by radiography.ResultsOverall, the levels of suPAR did not differ significantly between JIA patients and controls but those with polyarticular involvement showed higher suPAR (p = 0.013). In addition, elevated suPAR were associated with joint erosions (p = 0.026). Two RF/anti-CCP negative individuals with erosions showed high levels of suPAR.ConclusionsWe present new data on the biomarker suPAR in JIA. Our results indicate that, apart from RF and anti-CCP, analysis of suPAR could be of additional value in assessing the risk of erosions. Analysis of suPAR early could potentially guide treatment decision-making in JIA, but our observations should be confirmed in prospective studies.
33.	Lundberg, Veronica, et al. (author) Health-related quality of life among Swedish children with Juvenile Idiopathic Arthritis : parent-child discrepancies, gender differences and comparison with a European cohort 2017 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 15 Journal article (peer-reviewed)abstract Background: This study investigates gender differences in self-reports and between parent and child reports in Healthrelated Quality of Life (HRQOL), measured with disease-specific and generic instruments for chronic disease. Comparison of HRQOL results in this Juvenile Idiopathic Arthritis (JIA) sample to a European cohort of children with JIA and one of children with other health conditions are also made. Methods: Fifty-three children with juvenile idiopathic arthritis (JIA), aged 8-18 years, and their parents completed the condition-specific DISABKIDS for JIA, and the DISABKIDS generic instrument for chronic conditions (DCGM-37) in a cross-sectional study. European reference data were used for comparison of child and parental reports. Results: Child self-reports in DCGM-37 and DISABKIDS for JIA showed no gender differences. Parental and child reports of the child's HRQOL differed only in DCGM-37; this was among girls who scored their independence (p = 0.03), physical limitation (p = 0.01), social exclusion (p = 0.03), emotions (p < 0.01), and general transformed score (p < 0.01) higher than did their parents. Our sample of children with JIA reported more physical limitation compared to samples of European children with JIA (p = 0.01), European children with chronic conditions (p < 0.01), and their parents (p = 0. 01 and p < 0.01). The Swedish children reported more problem with understanding compared to the European JIA sample (p = 0.03). Swedish parents perceived their children's independence significantly lower than did the European parents of JIA children (p < 0.01), as well as European parents of children with chronic conditions (p = 0.03). The Swedish parents also perceived their children to have significantly lower social inclusion (p < 0.05) and general transformed score (p = 0.04), in comparison to European parents of children with chronic conditions. Conclusions: Parent-child differences in assessment of quality of life depend on the HRQOL instrument used, especially among girls. In comparison to European cohorts, our sample of children with JIA experienced more physical limitations and less understanding.
34.	Lundberg, Veronica, et al. (author) How children with juvenile idiopathic arthritis view participation and communication in healthcare encounters: a qualitative study 2021 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Journal article (peer-reviewed)abstract Background: Children report that they do not participate in their healthcare as much as they want, despite having the lawful right to form their own views and the right to express those views freely in all matters affecting them. Children and parents appeared to be more satisfied when healthcare professionals (HCP) use a participatory style in healthcare encounters.Aim: To explore how children, adolescents and young adults with Juvenile Idiopathic Arthritis (JIA) and parents of children with JIA view their participation and communication in healthcare encounters with healthcare professionals.Methods: Using a qualitative study design, participatory workshops were held separately for children and young adults with JIA and parents of children with JIA. The workshop data were analysed with Graneheim and Lundman’s Qualitative Content Analysis resulting in one main theme and two subthemes.Results: The theme “Feeling alienated or familiar with healthcare encounters” illuminates how children felt alienated at healthcare encounters if they found the encounters emotionally distressing. Children could withhold information regarding their health and function from both HCPs and their family and friends. The subtheme “Distancing oneself from healthcare” describe why children felt reluctant to engage in the healthcare encounters and experienced difficulty expressing how they really felt. The subtheme “Being a normal event in life” describe how children felt more comfortable over time engaging with HCPs when they knew what would happen, and felt that HCPs gave them the necessary support they needed to participate. Conclusions: Children’s participation in healthcare encounters varied depending if children felt alienated or familiar to the healthcare situations. Children distance themselves and are reluctant to engage in healthcare encounters if they find them emotionally distressing and feel disregarded. Over time, children can become more familiar and at ease with healthcare situations when they feel safe and experience personal and positive encounters. When the children are prepared for the encounter, provided with the space and support they want and receive tailored help they are more enabled to participate.
35.	Mikola, K., et al. (author) Transitioning patients with juvenile idiopathic arthritis to adult care: the Nordic experience 2022 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20:1 Journal article (peer-reviewed)abstract Background With juvenile idiopathic arthritis (JIA), there are several protocols and practices used worldwide for the transition from paediatric to adult care. In this study, we examined the transferral rates and disease activity after transition, as well as the disease- and health-related outcomes. We also introduce the transition practices employed in the Nordic countries. Methods The study population comprised 408 participants with a disease onset from 1997 to 2000 who attended an 18-year follow-up visit in this population-based Nordic JIA cohort study. The patients were retrospectively divided into three subgroups: Patients transferred directly from paediatric care to adult rheumatology care, patients referred there later, and patients never transferred during the 18-year follow-up period. Results One hundred and sixty-three (40%) JIA patients had been directly transferred to an adult clinic. The cumulative transition rate was 52%, but there were significant differences between the participating centres. Fifty patients had later been referred to an adult clinic. Among the 195 patients who had never been transferred, 39% were found to have disease activity at the study visit. Conclusion This study highlights the need to reconsider transition practices to avoid our undesirable finding of patients with disease activity in JIA, but no appropriate health care follow-up.
36.	Nordal, E., et al. (author) Incidence and predictors of Uveitis in juvenile idiopathic arthritis in a Nordic long-term cohort study 2017 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 15 Journal article (peer-reviewed)abstract Background: The incidence of uveitis associated with juvenile idiopathic arthritis (JIA) varies around the world. Our aim was to investigate the incidence and predictors of uveitis in a Nordic population-based cohort. Methods: Consecutive JIA cases from defined geographical areas in Denmark, Finland, Sweden and Norway with disease onset between January 1997 to June 2000 were followed for median 98 months in this prospective longitudinal cohort study. Potential clinical and immunological predictors of uveitis were identified with logistic regression analysis. Results: Uveitis occurred in 89 (20.5%) of the 435 children with regular ophtalmologic follow-up among the 500 included. Chronic asymptomatic uveitis developed in 80 and acute symptomatic uveitis in 9 children. Uveitis developed at a median interval of 0.8 (range - 4.7 to 9.4) years after onset of arthritis. Predictors of uveitis were age < 7 years at JIA onset (Odds ratio (OR) 2.1, 95% confidence interval (CI) 1.3 to 3.5), presence of antihistone antibodies (AHA) > 15 U/ml (OR 4.8 (1.8 to 13.4)) and antinuclear antibodies (ANA) (OR 2.4 (1.5 to 4.0)). Mean combined IgM/IgG AHA was significantly higher in the uveitis group (19.2 U/ml) than in the non-uveitis group (10.2 U/ml) (p = 0.002). Young age at JIA onset predicted uveitis in girls (p < 0.001), but not in boys (p = 0.390). Conclusion: Early-onset arthritis and presence of AHA in girls, as well as presence of ANA in both genders, were significant predictors of chronic uveitis. The high incidence of uveitis in this long-term Nordic JIA cohort may have severe implications in a lifelong perspective.
37.	Nordal, E., et al. (author) Participation in school and physical education in juvenile idiopathic arthritis in a Nordic long-term cohort study 2019 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 17 Journal article (peer-reviewed)abstract BackgroundThe aim of the study was to describe school attendance and participation in physical education in school among children with juvenile idiopathic arthritis (JIA).MethodsConsecutive cases of JIA from defined geographical areas of Finland, Sweden and Norway with disease onset in 1997 to 2000 were followed for 8 years in a multi-center cohort study, aimed to be as close to population-based as possible. Clinical characteristics and information on school attendance and participation in physical education (PE) were registered.ResultsParticipation in school and in PE was lowest initially and increased during the disease course. Eight years after disease onset 228/274 (83.2%) of the children reported no school absence due to JIA, while 16.8% reported absence during the last 2 months due to JIA. Full participation in PE was reported by 194/242 (80.2%), partly by 16.9%, and none by 2.9%. Lowest participation in PE was found among children with ERA and the undifferentiated categories. Absence in school and PE was associated with higher disease activity measures at the 8-year visit. School absence >1day at baseline predicted use of disease-modifying anti-rheumatic drugs, including biologics (DMARDs) (OR 1.2 (1.1-1.5)), and non-remission off medication (OR 1.4 (1.1-1.7) 8 years after disease onset.ConclusionSchool absence at baseline predicted adverse long-term outcome. In children and adolescents with JIA participation in school activities is mostly high after 8years of disease. For the minority with low participation, special attention is warranted to promote their full potential of social interaction and improve long-term outcome.
38.	Nordal, EB, et al. (author) PReS-FINAL-2046: Uveitis in the Nordic juvenile idiopathic arthritis cohort; high incidence, frequent complications, and gender-associated risk factors 2013 In: Pediatric Rheumatology. - 1546-0096. ; 65:Suppl. 10, s. S124-S124 Journal article (peer-reviewed)
39.	Rydenman, Karin, 1982, et al. (author) Epidemiology and clinical features of PFAPA: a retrospective cohort study of 336 patients in western Sweden 2022 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20 Journal article (peer-reviewed)abstract Background: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is generally regarded as the most common autoinflammatory disease, but the epidemiology of the disease is largely unknown. The objectives of this study were to estimate the annual incidence and describe the clinical features of PFAPA in a large cohort from western Sweden. Methods: The study retrospectively included children < 18 years of age diagnosed with PFAPA between 2006 and 2017 at three hospitals: NU Hospital Group, Skaraborg Hospital and Queen Silvia Children’s Hospital. Patients were identified by searching for relevant diagnostic ICD-10 codes in the comprehensive electronic medical records and data were retrieved by reviewing case records. To estimate incidence, patients with symptom onset from January 1, 2006, to December 31, 2016, were included. Population data for the study area during this period were retrieved from Statistics Sweden. Results: In this study, 336 patients with PFAPA were identified. Of these, 156 (46%) were girls and 180 (54%) were boys. Almost 90% of the children with PFAPA (291 patients) experienced their first symptoms before the age of 5 years and fewer than 3% presented at ages above 10 years. Pharyngitis was the most common symptom during febrile episodes, followed by cervical adenitis and aphthous stomatitis. Fourteen percent of the patients displayed atypical features, of which skin rash was the most common. To calculate incidence, 251 patients with symptom onset during the study period were identified. The mean annual incidence was estimated at 0.86/10,000 for children < 18 years of age and 2.6/10,000 for children < 5 years of age. Conclusions: This study adds to the understanding of the epidemiology of PFAPA syndrome by presenting incidence rates based on a large cohort and in different age groups in a population-based setting. It also shows the distribution of age of onset of PFAPA, with a peak in 1-year-olds and waning at older ages. Signs and symptoms of PFAPA syndrome were similar in children with symptom onset before vs. after 5 years of age.
40.	Skarin, Angelika, et al. (author) Uveitis associated with juvenile arthritis : a continued cohort study 40 years after uveitis onset 2022 In: Pediatric Rheumatology. - : Springer Science and Business Media LLC. - 1546-0096. ; 20:1 Journal article (peer-reviewed)abstract BACKGROUND: A third follow-up study, mean 40.7 years after uveitis onset, of a cohort originally consisting of 55 Swedish patients with uveitis associated with juvenile arthritis.METHOD: A retrospective study of the patients' ophthalmic medical records. The results were compared to those of the same cohort previously studied at mean 7.2 and 24.0 years after uveitis onset. In the present follow-up study, 30 of the original 55 patients consented to participate. Of these, 26 had ophthalmic medical records that were reviewed.RESULTS: In the 30 participants, active uveitis was seen in 43.4%, cataracts in 66.6% and glaucoma in 40.0%. When comparing data from previous follow-ups of the same cohort, a total of 61.8% were reported to have had cataracts at any of the three follow-ups, 29.0% had glaucoma or ocular hypertension and 12.7% had severe visual impairment in both eyes. At mean 40.7 years after uveitis onset 20% of patients in the original uveitis cohort were deceased. In 4 of the 11 deceased individuals, rheumatic disease was stated as the main cause of death, and in 3 it was considered a contributory factor in the patients deaths.CONCLUSIONS: Uveitis associated with juvenile arthritis can be active into midlife and possibly longer. Ocular complications and visual loss increased up to 40 years after uveitis diagnosis. The mortality rate of this cohort was higher than that of a corresponding Swedish population. Lifelong ophthalmic check-ups are probably necessary for patients diagnosed with this type of uveitis.
41.	Tuomi, Anna-Kaisa, et al. (author) Body mass index is associated with health-related quality of life and disease characteristics in young adults with juvenile idiopathic arthritis 2024 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 22:1 Journal article (peer-reviewed)abstract Background There is a growing interest concerning the relationship between obesity and several medical conditions and inflammation. Nevertheless, there is a lack of studies regarding body mass index (BMI) among patients with juvenile idiopathic arthritis (JIA). Our aim was to investigate the impact of BMI on health-related quality of life (HRQoL) measured with a 36-Item Short Form Survey (SF-36), disease activity, and disability in young adults with JIA. Methods This study is a part of the population-based Nordic JIA cohort study. All newly diagnosed patients with JIA were recruited consecutively between 1997-2000 in specific regions in the Nordic countries. Patients in this sub-study were enrolled from 434 patients who attended their 18-year follow-up visit. Patients were classified according to the World Health Organization (WHO) into four groups based on their BMI. HRQoL, disease characteristics, disability, fatigue, sleep quality, physical activity, pain, comorbidities, and social status were assessed. Results Three hundred fifty-five patients from the original study cohort were enrolled in this study and 72% of them were female. Mean age was 23.9 (+/- SD 4.4) years. A significant relationship was found between the JIA categories and BMI groups (p = 0.014). A significant relationship was also found between BMI and disease activity scores (DAS28) (p = 0.028), disability (p < 0.001), pain (p = 0.013), fatigue (p = 0.035), and sleep quality (p = 0.044). Moreover, a significant relationship between BMI and HRQoL regarding bodily pain (p = 0.010) and general health (p = 0.048) was revealed when adjusted for sex, age, and JIA subtype. Conclusion We discovered that BMI was significantly related to HRQoL, disease activity, and disability. BMI deserves more attention considering the treatment options and outcome of JIA in young adults.
42.	Öman, Anders, 1975-, et al. (author) Fecal microbiota in children with juvenile idiopathic arthritis treated with methotrexate or etanercept 2021 In: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 19:1 Journal article (peer-reviewed)abstract BackgroundAlterations in the composition of the fecal microbiota in children with juvenile idiopathic arthritis (JIA) have been observed in several studies, but it has not been determined whether the standard treatment for JIA changes the composition or function of the microbiota.The first-line disease-modifying anti-rheumatic drug for treatment of JIA is usually methotrexate, followed or supplemented by anti-tumor necrosis factor alpha drugs, such as etanercept. The aim of this study was to investigate the effects of methotrexate and etanercept treatments on the fecal microbiota and the fecal short-chain fatty acids (SCFAs) in children with JIA.MethodsIn this multicenter study, the composition of fecal microbiota from 45 treatment-naïve children with JIA was compared with that from 29 children treated with methotrexate and 12 children treated with etanercept. We also made pairwise comparisons of 15 children sampled before and during methotrexate treatment and 7 children sampled before and during etanercept treatment.The microbiota was determined using sequencing amplicons from the V3 and V4 regions of the 16S rRNA gene. Alpha-diversity, community composition, and relative abundances of bacterial taxa were analyzed in all comparisons. Analyses of fecal SCFAs, using a high-performance liquid chromatograph, were performed for the pairwise comparisons.ResultsWe did not find any significant differences in α-diversity or community composition of microbiota. However, principal coordinate analysis indicated a change in community composition in 7 of the 15 paired samples before and during methotrexate and 2 of the 7 paired samples before and during etanercept.Comparisons of the relative abundance of taxa revealed minor differences before and during treatment with methotrexate or etanercept, but they were not significant after correction for multiple analyses, and the unpaired and paired analyses did not show similar changes.There were no significant differences in levels of fecal SCFAs before and during treatment with methotrexate or etanercept.ConclusionsTreatment with methotrexate or etanercept had minor, but no significant or consistent changes either on composition of microbiota or on levels of SCFAs, suggesting that these changes are not related to the therapeutic effects of methotrexate or etanercept.

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