Uveitis in Juvenile Idiopathic Arthritis: 18-Year Outcome in the Population-based Nordic Cohort Study.

PURPOSE: To assess the long-term outcome of uveitis in juvenile idiopathic arthritis (JIA). DESIGN: Population-based, multicenter, prospective JIA cohort, with a cross-sectional assessment of JIA-associated uveitis (JIA-U) 18 years after the onset of JIA. PARTICIPANTS: A total of 434 patients with JIA, of whom 96 had uveitis, from defined geographic areas of Denmark, Finland, Norway, and Sweden. METHODS: Patients with onset of JIA between January 1997 and June 2000 were prospectively followed for 18 years. Pediatric rheumatologists and ophthalmologists collected clinical and laboratory data. MAIN OUTCOME MEASURES: Cumulative incidence of uveitis and clinical characteristics, JIA and uveitis disease activity, ocular complications, visual outcome, and risk factors associated with the development of uveitis-related complications. RESULTS: Uveitis developed in 96 (22.1%) of 434 patients with JIA. In 12 patients (2.8%), uveitis was diagnosed between 8 and 18 years of follow-up. Systemic immunosuppressive medication was more common among patients with uveitis (47/96 [49.0%]) compared with patients without uveitis (78/338 [23.1%]). Active uveitis was present in 19 of 78 patients (24.4%) at the 18-year visit. Ocular complications occurred in 31 of 80 patients (38.8%). Short duration between the onset of JIA and the diagnosis of uveitis was a risk factor for developing ocular complications (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.8). Patients with a diagnosis of uveitis before the onset of JIA all developed cataract and had an OR for development of glaucoma of 31.5 (95% CI, 3.6-274). Presence of antinuclear antibodies (ANAs) was also a risk factor for developing 1 or more ocular complications (OR, 3.0; 95% CI, 1.2-7.7). Decreased visual acuity (VA) <6/12 was found in 12 of 135 eyes (8.9%) with uveitis, and 4 of 80 patients (5.0%) with JIA-U had binocular decreased VA <6/12. CONCLUSIONS: Our results suggest that uveitis screening should start immediately when the diagnosis of JIA is suspected or confirmed and be continued for more than 8 years after the diagnosis of JIA. Timely systemic immunosuppressive treatment in patients with a high risk of developing ocular complications must be considered early in the disease course to gain rapid control of ocular inflammation.

Increasing prevalence of coeliac disease in Denmark: a linkage study combining national registries.

AIM: To determine the prevalence and incidence of diagnosed coeliac disease (CD) in Danish children and adolescents and to describe trends over time. METHODS: All children with a CD diagnosis registered in the Danish National Patient Registry (DNPR) were included in the study. Data were validated by combining this information with registrations of small-bowel biopsies in the National Registry of Pathology (NRP) and with a selected sample of hospital records. RESULTS: Data were obtained from 1996 to 2010. The prevalence of CD registered in DNPR increased from 43.2 [95% CI 39.3-47.1] to 83.6 [95% CI 78.4-88.7] per 100,000, and the incidence increased from 2.8 [95% CI 1.9-3.9] to 10.0 [95% CI 8.4-12.0] per 100,000; 56% of the children had at least one biopsy compatible with CD registered in NRP. The incidence of biopsy-verified CD increased from 0.8 [95% CI 0.3-1.4] to 6.9 [95% CI 5.4-8.4] per 100,000. The mean age at diagnosis increased from 5.1 [95% CI 3.5-6.6] to 8.1 [95% CI 7.2-9.0] years of age. The proportion of children with associated diseases did not change over time. CONCLUSION: The prevalence of diagnosed CD in Danish children and adolescents has increased over the last 15 years.

Response to influenza vaccination in immunocompromised children with rheumatic disease: a prospective cohort study.

BACKGROUND: Prevention of illness due to infection by influenza viruses is important for children with rheumatic diseases. Biological disease modifying antirheumatic drugs have become increasingly important in the treatment of juvenile idiopathic arthritis, and combinations of immunosuppressive drugs are used for the treatment of systemic disorders, which increase the risk of secondary immunodeficiency. Therefore, we investigated whether children with rheumatic disease can mount a protective antibody response after influenza immunization. METHODS: The prospective multicentre cohort study was conducted in Denmark during the influenza season 2015-2016. Children with rheumatic disease aged six months to 19 years were eligible. Controls were immunologically healthy children. A blood sample was collected before and after vaccination and analysed by haemagglutination inhibition (HI) assay for the 2015-2016 influenza vaccine-strains. In case of flu-like symptoms the child was tested for influenza. For statistical analyses the patients were grouped according to medical treatment or disease. RESULTS: A total of 226 patients and 15 controls were enrolled. No differences were found for the increase of antibodies from pre-vaccine to post-vaccine between the groups in our primary analyses: A/Cal H1N1pdm09 (p = 0.28), A/Swi H3N2 (p = 0.15) and B/Phu Yamagata (p = 0.08). Only when combining patients across groups a lower increase in antibodies was found compared to controls. Among all patients the pre-vaccine rates for seroprotection using the HI-titer cut-off ≥ 40 were 93.1-97.0 % for all three strains. For seroprotection using the HI-titer cut-off ≥ 110 the pre-vaccine rates for all patients were 14.9-43.6 % for all three strains and an increase in the proportions of patients being seroprotected after vaccination was found for A/Cal H1N1pdm09 and A/Swi H3N2. None of the children with flu-like symptoms tested positive for the vaccine strains. CONCLUSIONS: Children with rheumatic diseases increase in antibody titres after influenza immunization, however, it remains uncertain whether a protective level is achieved.

Positive predictive value of serological diagnostic measures in celiac disease.

BACKGROUND: Celiac disease (CD) antibodies, immunoglobulin A (IgA) anti-tissue transglutaminase (anti-tTG), IgA endomysium antibody (EMA), IgA and IgG anti-gliadin antibodies (IgA and IgG AGA) are first-line diagnostic tools used in selecting patients for duodenal biopsy. The goal of this study was to evaluate the diagnostic quality of serological testing for CD. METHODS: CD serological tests (IgA and IgG AGA, anti-tTG and EMA) from 11,915 individuals were measured. Data were combined with clinical data and results of duodenal biopsy using a unique Danish personal identification number. RESULTS: The positive predictive value (PPV) varied according to different combinations of positive CD antibodies, being highest when all antibodies were positive (97.6%). The anti-tTG concentration correlated strongly with EMA positivity, number of additional positive antibodies, and higher PPV. A logistic regression model predicted the probability of later biopsy-proven CD in relation to concentrations of IgA AGA and anti-tTG at initial serological screening. CONCLUSIONS: The anti-tTG concentration at initial serological CD screening was highly informative in relation to EMA positivity, number of additional CD specific antibodies and PPV. Furthermore, in the high-risk group of patients investigated, the concentrations of anti-tTG and IgA AGA at initial serological screening could accurately predict the probability of future biopsy-proven CD.

[Multisystem inflammatory syndrome in children after SARS-CoV-2 infection].

In the era of the coronavirus disease pandemic, a new disease entity named multisystem inflammatory syndrome in children has emerged. This is a case report of a seven-year-old boy with hyperinflammation and cardiac involvement, compatible with this disease entity. Antibody tests and symptoms indicated previous severe acute respiratory syndrome coronavirus 2 infection. The patient was treated according to international guidelines with full symptom resolution. Awareness of this inflammatory syndrome should prompt immediate treatment and could possibly avoid fatal outcomes.

Long-Term Outcomes in Juvenile Idiopathic Arthritis: Eighteen Years of Follow-Up in the Population-Based Nordic Juvenile Idiopathic Arthritis Cohort.

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.

Longterm Outcomes of Temporomandibular Joints in Juvenile Idiopathic Arthritis: 17 Years of Followup of a Nordic Juvenile Idiopathic Arthritis Cohort.

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.

Questionnaire-based case finding of celiac disease in a population of 8- to 9-year-old children.

OBJECTIVE: Antibody screenings and diagnosis of celiac disease (CD) among children with type 1 diabetes have suggested that a considerable proportion of children with CD may, in fact, have preclinical (undiagnosed) symptoms. We aimed to test if a questionnaire would lead to significant case finding in an unselected population of 8- to 9-year-old children. PATIENTS AND METHODS: The study population included 9880 children aged 8 to 9 years. Before the study, 13 children from the study population were known to have CD. We developed a questionnaire on the basis of 5 simple items suggestive of CD and mailed the questionnaire to the families of all children in the study population who resided in the County of Funen, Denmark. In total, 7029 respondents returned the questionnaire (70%); among them, 2835 children had 1 or more symptoms. These children were invited for a blood test to determine their human serum immunoglobulin A (IgA) anti-tissue transglutaminase antibody (anti-tTG) levels. RESULTS: Of the 1720 children who were tested for the human serum IgA anti-tTG, 24 participants had a positive result (range: 20 to >150 U). Seventeen of these children underwent an upper endoscopy procedure. Fourteen children had histologic signs of CD (Marsh classification stage III). Fourteen children met the diagnostic criteria for CD. The prevalence proportion of patients who were newly diagnosed with CD was 0.14% (95% CI: 0.08-0.24) (14 of 9967), and the estimate of the minimum total prevalence proportion of children with CD was 0.27% (95% CI: 0.18-0.39) (27 of 9980). The maximal prevalence proportion of patients with newly diagnosed CD was 1.22% (95% CI: 0.76-1.90) (21 of 1720), including those participants who had a positive anti-tTG result but not a final diagnosis of CD. The ratio of known to minimally symptomatic CD was approximately 1:1. CONCLUSION: A number of preclinical and low-grade symptomatic patients with CD may be identified by their responses to a mailed questionnaire.