The Temporomandibular Joint in Juvenile Idiopathic Arthritis : Psychosocial, clinical, imaging and parotid saliva biomarkers

Sammanfattning: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The disease can affect the temporomandibular joint (TMJ) and cause orofacial growth disturbances, pain, and jaw dysfunction. TMJ arthritis is often asymptomatic and therefore a challenging joint to diagnose. Clinical assessment of the TMJ is hampered by the low sensitivity and specificity of joint pain and the absence of physical findings early in the disease process. More specific methods are therefore needed for diagnosing TMJ arthritis. Saliva and blood are promising as diagnostic fluids for various diseases. Also, adolescents with chronic pain report high rates of psychosocial stress. Psychosocial stress may also be involved in JIA as a trigger and maintaining factor of the disease. Aim: The main aim of this thesis research was to investigate the relation between clinical variables, psychosocial factors, MRI findings, and inflammatory biomarkers in saliva and blood in relation to TMJ involvement in JIA. The secondary aim was to investigate the relation between stress and change in stress over time in comparison with orofacial pain, psychosocial factors, and jaw function in JIA patients. Methods: This was a cross-sectional case-control study and a longitudinal cohort study. Forty-five patients (6-16 years old) with JIA and 16 healthy age- and sex-matched healthy individuals were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The study subjects completed questionnaires regarding psychosocial factors and underwent bilateral MRI of their TMJs. Unstimulated parotid saliva and venous blood samples were collected. Biochemical analyses were performed using a multiplex platform electrochemiluminescence assay from Meso Scale Discovery (MSD) for measuring cytokine concentrations in saliva and blood. A two-year prospective follow-up study was performed in 40 JIA patients from our original baseline study. The JIA patients underwent the same clinical examination and completed the same questionnaires regarding psychosocial factors as in the baseline studies. Results: The JIA patients with orofacial pain had higher degrees of stress, depression, catastrophizing, and jaw dysfunction than did those JIA patients without such pain. These factors were also associated with orofacial pain intensity. Additionally, patients with orofacial pain had higher systemic inflammatory activity. In the two-year follow-up study, we observed that change in stress was associated with changes in catastrophizing, psychological distress, as well as limitations in both general and jaw functions. Regarding TMJ MRI findings, there were no significant differences between JIA patients and healthy individuals in either the inflammatory or damage domain. Moderate/severe TMJ changes in the inflammatory and damage domains were, however, only found in the JIA patients. Among JIA patients, orofacial pain intensity was correlated to TMJ bone marrow edema, and pain in jaw muscles during jaw function was related to both TMJ bone marrow edema and erosion. JIA patients had lower concentrations of interleukin receptor 6 (IL-6R) and glycoprotein 130 (gp130) in parotid saliva than in plasma. Higher concentrations of IL-6 were found in parotid saliva than in plasma. The members of the interleukin-6 family (i.e., IL-6, IL-6R, and gp130) in parotid saliva were found to be explanatory factors for the presence of bone marrow edema and effusion in the JIA patients. 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 aspect related to these factors. Increased disease activity with more joint involvement seems to be an important factor contributing to orofacial pain in JIA. Myalgia, in addition to arthritis, seems to be an important source of orofacial pain in these patients. Maintaining a low stress level in JIA patients seems to be crucial, as an increase in stress level over a two-year period appears to negatively impact both jaw function as well as psychosocial distress and catastrophizing. There was an overlap of TMJ MRI findings regarding signs of inflammatory and bone tissue changes between JIA patients and healthy individuals. Among, JIA patients, the presence of inflammatory MRI signs, and bone marrow edema seems to worsen orofacial pain intensity. The IL-6 family in parotid saliva is associated with TMJ bone marrow edema and effusion in patients with JIA, suggesting that IL-6 has promising properties as a parotid saliva biomarker of TMJ inflammatory activity. In addition there seems to be local production of the IL-6 family in the parotid gland in JIA patients and healthy individuals. However, parotid saliva does not seem to reflect the plasma content in terms of the investigated biomarkers in JIA.