The Pediatric Research Group has several ongoing projects in pediatric rheumatology. Some of these include:

1. The Nordic JIA Cohort (BART):

   • Project Leader at UNN: Ellen Nordal
   • Project Collaborators: Senior Consultant Nils Thomas Songstad, Pediatric Rheumatologist Veronika Rypdal, and Study Nurse Tonje Løvli.

   This project focuses on following patient cohorts with juvenile idiopathic arthritis (JIA) to gain knowledge about the natural course and prognosis of the disease. The "BART Nordic Juvenile Arthritis Study" involves 500 Nordic children under 16 years, creating a database with extensive clinical data and blood values. It provides a unique opportunity to examine the disease course and occurrence of JIA and associated uveitis in a well-defined group of children followed over many years.
   
   Sub-Studies:

• "From childhood to adulthood with juvenile arthritis: Disease activity scores, uveitis, and prediction models for severe disease course" is led by Postdoctoral Researcher Veronika Rypdal and Associate Professor/Senior Consultant Ellen Nordal.

The follow-up, which concluded in 2018, spans eighteen years after the onset of the disease. The project focuses on validating the use of different disease activity scores during the transition from childhood to adulthood. The study explores the occurrence, risk factors, and complications of uveitis/iritis. A prediction model based on baseline data to predict the likelihood of not achieving disease-free remission, obtaining lasting damage, or experiencing reduced functional capacity is currently in development.

Data collected from clinical monitoring by pediatricians, ophthalmologists, and dentists throughout the Nordic region are being analyzed. Biological material, including serum, EDTA-blood, and joint fluid, is part of a large international consortium studying the genetic predisposition for juvenile arthritis.

2. The Norwegian JIA Study (NorJIA):

   • Project Leader at UNN: Ellen Nordal
   • Project Collaborators: Senior Consultant Nils Thomas Songstad, Study Nurse Tonje Løvli, PhD candidates Paula Frid, Veronika Rypdal, Thomas Augdal M.D., and Josefine Halbig D.D.
     
     

   NorJIA is a prospective, multisite observational study involving 227 children with juvenile idiopathic arthritis (JIA) and an equal number of healthy controls. The study is conducted at university clinics in Bergen, Tromsø, and Trondheim. It spans over 5 years, encompassing expanded clinics, laboratory examinations, radiology, and oral examinations at baseline and during the 2-year follow-up. The study places particular emphasis on the temporomandibular joint with extended radiology, including 3Tesla magnetic resonance tomography (MR), ultrasound, and CBCT (computer tomography of the temporomandibular joint). Clinical examinations are conducted with the intention of establishing scoring systems for active and chronic inflammation.

SUB-STUDIES;

Cytokine profile in serum, saliva, and synovial fluid from the temporomandibular joint in JIA. A norwegian multi-center pilot study (Oralkirurg Paula Frid, Førsteamanuensis/ overlege Ellen Nordal)

The purpose of this pilot study is to investigate the effectiveness and safety of temporomandibular joint injections with steroids in children with juvenile idiopathic arthritis (JIA) suffering from temporomandibular joint arthritis. The study also includes microbiological and immunological examinations of temporomandibular joint fluid and saliva. The study is conducted as an observational study.

The medication Lederspan® will be administered in two different doses depending on the child's weight. The injection will be performed either under general anesthesia or local anesthesia. Before and after the treatment, assessments will be made regarding jaw opening capacity, pain levels, and findings from magnetic resonance imaging (MRI) of the temporomandibular joint.

The study aims to include a total of 20-25 patients under the age of 18 from Tromsø, Trondheim, Bergen, Oslo, and Århus. Biological samples, including saliva, serum, EDTA-blood, and joint fluid, will be analyzed for cytokine profiles and saliva for oral microbiota.

Temporomandibular Joint Arthritis in Juvenile Arthritis: Validation of Clinical Findings and Imaging Diagnosis in a Norwegian Multicenter Cohort Study. (PhD Student: Thomas Augdal, Principal Supervisor: Ellen Nordal)

The rapid advancements in modern imaging diagnostics have provided better opportunities to visualize joints in general and, particularly, the temporomandibular joint. While CBCT (Cone Beam Computed Tomography) reveals fine details in the skeletal structure, MRI (Magnetic Resonance Imaging) can offer detailed information about the bone marrow, joint fluid, and the soft tissues surrounding the joint. There is particular anticipation regarding whether the commercially available MRI technology can accurately show whether there is active joint inflammation or not.

However, standardized, validated, and feasible assessment systems are currently lacking. Additionally, there is insufficient knowledge about the normal growth and development of the temporomandibular joint in children. In this prospective, longitudinal cohort study, the university clinics in Bergen, Trondheim, and Tromsø will collectively examine children with Juvenile Idiopathic Arthritis (JIA) to:

1. Identify imaging biomarkers for active and chronic disease in the temporomandibular joints.
2. Develop a scoring system for MRI in active and chronic disease.
3. Validate the biomarkers and scoring system using a comprehensive diagnostic approach.
4. Examine dental and bone health in children with JIA.

Oral Health-Related Quality of Life among Children and Youth with Arthritis in Norway (PhD Student: Josefine Mareile Halbig, Principal Supervisor: Ellen Nordal)

Health-related quality of life is a multidimensional concept encompassing overall health status and an individual's perception of their health, illness, and/or functional ability. The World Health Organization (WHO) considers oral health-related quality of life as an integral part of both oral and general health. The main objective of this study is to enhance knowledge about oral health and oral health-related quality of life among children and youth with arthritis to improve diagnosis, follow-up, and treatment.

Temporomandibular joint arthritis and temporomandibular dysfunction are common findings in children with arthritis. Temporomandibular dysfunction and pain can reduce both daily functional capacity and quality of life. Temporomandibular joint involvement, with or without growth disturbance, often leads to issues with chewing, mouth opening, and thorough teeth brushing. This can result in diminished oral health-related quality of life.

The study plans to publish three papers with the following specific goals:

• Investigate oral health and oral health-related quality of life and changes in these aspects over a two-year period among children and youth with Juvenile Idiopathic Arthritis (JIA) compared to healthy controls.
• Examine the occurrence of gingivitis and periodontitis in relation to medication and oral health-related quality of life in children and youth with JIA and healthy controls.
• Describe the prevalence of temporomandibular dysfunction (TMD) in children and youth with JIA and healthy controls, map changes in TMD over a two-year period, and examine the impact of TMD on oral health-related quality of life.
• Investigate jaw growth in cases of temporomandibular joint involvement.

3. Pharmacological Monitoring in Patients with Juvenile Idiopathic Arthritis (Pharmachild) (Project Leader at UNN: Ellen Nordal, Project Collaborators: Senior Consultant Nils Thomas Songstad, Specialist Physician Veronika Rypdal, Nurse Tonje Løvli)

   Pharmachild is a multicenter cohort study aimed at monitoring side effects and long-term effects of medical treatment for juvenile idiopathic arthritis (JIA) with methotrexate and biologic drugs. This is an internationally funded project by the European Union, conducted under the auspices of the Pediatric Rheumatology International Trials Organisation (PRINTO http://www.printo.it/), planned to run for 10 years from 2013. Globally, it involves 9,137 children from various countries. In Norway, a total of 330 children and adolescents with JIA receiving treatment at Rikshospitalet OUS, St. Olavs Hospital, and University Hospital of North Norway are participating in the study.
   
   

4. MinJIA - Personalized Treatment for Juvenile Idiopathic Arthritis (Project Leader at UNN: Ellen Nordal, Project Collaborators: Senior Consultant Nils Thomas Songstad, Specialist Physician Veronika Rypdal, Research Nurse Tonje Løvli)

   MinJIA is a Norwegian multicenter randomized controlled study with the primary objective of investigating whether joint injections with cortisone (triamcinolone hexacetonide) in combination with tumor necrosis factor (TNF) inhibitors are more effective than TNF inhibitors alone in children and adolescents with juvenile idiopathic arthritis (JIA). All health regions are participating, and the study is based at Oslo University Hospital. The main outcome measure is remission, which means no symptoms or signs of active disease. Does cortisone injections in inflamed joints provide an additional effect when starting TNF inhibitor treatment for juvenile idiopathic arthritis? Both possible outcomes of the study will have implications for clinical practice. If a strategy that includes joint injections proves to be superior, the MinJIA study will contribute to evidence-based recommendations with a greater emphasis on joint injections. If it turns out that cortisone injections in all inflamed joints are unnecessary when initiating TNF inhibitor treatment, clinical practice will change, sparing children, adolescents, and families from uncomfortable and time-consuming procedures, and reducing costs for society.
   
   

5. Eurofever

   Project Leader in Norway: Ellen Nordal, Project Collaborators: Senior Consultant Nils Thomas Songstad, Research Nurse Tonje Løvli, PhD Candidate Veronika Rypdal

   Eurofever is an international registry study that addresses the occurrence and clinical course of autoinflammatory diseases such as periodic fever syndromes, chronic non-bacterial osteomyelitis (CNO/CRMO), and other autoinflammatory conditions. In Norway, children and adolescents with autoinflammatory conditions who are treated at Rikshospitalet OUS, St. Olavs Hospital, and the University Hospital of North Norway are participating in the study.

6. Best Available Treatment for Paediatric Inflammatory Syndromes (PIMS) Temporally Associated with SARS-CoV-2 (BATS) (Prosject leader at UNN Ellen Nordal, Research Nurse Tonje Løvli)

This is a multisite registry study on COVID-associated illness in children and adolescents, specifically Pediatric Inflammatory Multisystem Syndrome (PIMS), also known as Multi-inflammatory Syndrome in COVID-19 (MIS-C).