Temporomandibular joint pain and tissue destruction in relation to inflammatory activity in rheumatoid arthritis

Sammanfattning: The general aim of this thesis was to study temporomandibular joint (TMJ) pain and bone tissue destruction in patients with rheumatoid arthritis (RA), in particular: pro- and anti?inflammatory cytokines, systemic inflammatory activity, and the impact of TMJ pain on daily activities and quality of life. This thesis comprises three parts. The aim of the first part was to investigate the impact of TMJ pain and inflammation on daily activities and quality of life in relation to systemic inflammatory activity. The aim of the second part was to investigate how local and systemic cytokine levels of tumor necrosis factor (TNF) and interleukin 1 (IL-­?1) interact to modulate TMJ pain in RA. And the aim of the third study was to investigate the relationship between inflammatory mediators in TMJ synovial fluid and blood versus bone tissue destruction by magnetic resonance imaging (MRI) of the TMJ. Each study in this thesis examined subjects from the same group of patients with a recent RA diagnosis. In the first study, 33 patients participated; in the second, 26; and in the third, 22. Each study performed similar clinical examinations. The patients rated their TMJ pain (resting, movement, loading and on palpation) on a scale from 0 to 10 and underwent MRI examination to assess signs of TMJ erosions. We obtained and analyzed TMJ synovial fluid samples for TNF, IL-­?1ra, anti-­?citrullinated protein antibodies (ACPA), and rheumatoid factor (RF) and blood samples for erythrocyte sedimentation rate (ESR), C-­?reactive protein (CRP), ACPA and RF. Studies I and II used non-­?parametric statistics (Mann-­?Whitney U-­?test, Spearman correlation) while Study III used parametric statistics (student’s t-­?test and Pearson correlation). A probability level of less than 0.05 was considered as significant. The first study found that TMJ pain intensity, together with systemic inflammatory activities, plays an important role in the impact of TMJ pain on daily living and quality of life in RA. The second study found that a high TNF to TNFsRII ratio in the synovial fluid of the TMJ was associated with TMJ pain on palpation in patients with RA. High levels of TNF were found to be associated with high levels of TNFsRII; however, increases in local cytokine control in the presence of elevated levels of TNF was likely insufficient to control or inhibit the inflammatory process. Presence of ACPA in TMJ synovial fluid was associated with elevated TNF levels but not with TNFsRII levels. The third study found that TNF in TMJ synovial fluid modulates TMJ bone tissue resorption in patients with RA. However, bone tissue destruction was associated with a low degree of endogenous cytokine control. In conclusion, TNF, including its endogenous control system, seems to be involved in TMJ inflammation, which results in TMJ pain and tissue destruction. In turn, TMJ pain has a negative impact on daily living and quality of life in patients with RA.