Reactive arthritis in relation to internal derangements of the temporomandibular joint: a case control study.

The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ.

Tumor necrosis factor mediates temporomandibular joint bone tissue resorption in rheumatoid arthritis.

OBJECTIVE: To investigate if TNF, IL-1 or their endogenous controls, in relation to ACPA, are associated with radiological signs of ongoing temporomandibular joint (TMJ) bone tissue resorption and disc displacement in RA patients. METHODS: Twenty-two consecutive outpatients with TMJ of RA were included. Systemic inflammatory activity was assessed by DAS28. The number of painful regions in the body and ESR, CRP, RF and ACPA were analyzed. TMJ synovial fluid and blood samples were obtained and analyzed for TNF, TNFsRII, IL-1ra, IL-1sRII and ACPA. The ratios between the mediators and their endogenous control receptors were used in the statistical analysis. Magnetic resonance imaging was performed in closed- and open-mouth positions and evaluated regarding disc position and presence of condylar and temporal erosions of the TMJ. RESULTS: A high TNF level in relation to TNFsRII in TMJ synovial fluid correlated to the degree of TMJ condylar erosion. A high IL-1ra level in relation to TNF in TMJ synovial fluid was also correlated to the degree of TMJ condylar erosion. The total degree of TMJ condylar erosion was correlated with the number of painful regions. CONCLUSION: This study indicates that TNF in TMJ synovial fluid mediates TMJ cartilage and bone tissue resorption in RA. The study also suggests that the degree of endogenous cytokine control is of importance for development of bone tissue destruction.

Expression of ß-defensin 4 on temporomandibular joint discs with anterior displacement without reduction.

OBJECTIVES: ß-defensin-4 is a member of antimicrobial peptides (APs) of the immunity system. This molecule has antimicrobial activity but it seems to be involved in articular inflammatory processes too, as it happens during osteoarthritic disease (OA). Considering the possible relation existing between (OA) and temporomandibular disorders (TMD), the aim of our study was to evaluate immunohistochemically the presence of ß- defensin-4 in pathological temporomandibular joint (TMJ) discs affected by internal derangement without reduction (ADDwoR). DESIGN: Eighteen TMJ-displaced disc specimens were considered in this study and were analysed by immunohistochemical evaluation. They were compared with a control sample of sixteen healthy discs and two scores, intensity of staining (IS) and extent score (ES) were estimated. RESULTS: Findings of our analysis showed a significant difference between control and study sample (P < 0.001). IS and ES of control sample and pathological sample were 1 and 4 respectively. CONCLUSION: Our results confirmed the presence of ß-defensin-4 in human TMJ discs affected by ADDwoR, hypothesing a possible role of this molecule in articular bone disruption.

MCP-1 production in temporomandibular joint inflammation.

Synovitis, which is characterized by the infiltration of inflammatory cells, often accompanies progression of temporomandibular joint disorder (TMD) symptoms. Because IL-1ß is elevated in synovial fluids obtained from TMDs, we hypothesized that IL-1ß-responsive genes in synoviocytes may help identify the putative genes associated with synovitis. Using microarray analysis, we found that monocyte chemoattractant protein-1 (MCP-1) mRNA levels were elevated in IL-1ß-stimulated synoviocytes. MCP-1 is a member of the chemokine superfamily. The production of MCP-1 was increased in synoviocytes treated with IL-1ß. When IL-1ß was injected into the cavities of rat TMJs, inflammatory cells and MCP-1-positive cells were detected in the synovial tissues. Furthermore, MCP-1 levels were higher in synovial fluids from individuals with pain compared with those without pain. Inhibitors of MAP-kinases and NF-κB reduced IL-1ß-induced MCP-1 production. These results suggest that MCP-1 stimulated by IL-1ß is one of the factors associated with the inflammatory progression of TMDs.

Increased levels of soluble cytokine receptors in the synovial fluid of temporomandibular joint disorders in relation to joint effusion on magnetic resonance images.

PURPOSE: The purpose of this study is to clarify the significance of joint effusion (JE) on T2-weighted magnetic resonance images of the temporomandibular joint (TMJ) in comparison to various soluble cytokine receptors in the synovial fluid of patients with temporomandibular disorders (TMDs). PATIENTS AND METHODS: Magnetic resonance imaging of 55 TMJs of 55 patients with TMD was performed, and synovial fluid samples were obtained on the same day. The grade of JE was evaluated on a scale from 0 to 3, with grade 0 indicating the absence of JE and grades 1 to 3 indicating the presence of JE. Correlations were measured between JE and the concentrations of soluble tumor necrosis factor receptors I and II, interleukin (IL) 6 soluble receptor, IL-1 soluble receptor type II, and IL-1 receptor antagonist and protein in the synovial fluid samples. RESULTS: The mean concentrations of cytokine receptors in the synovial fluid were significantly higher in the 30 joints with JE than in the 25 joints without JE. There were no correlations between the JE grade and the level of any mediators. CONCLUSION: Increased levels of cytokine receptors are likely to influence the expression of JE and may play important roles in the pathogenesis of TMD. These results also suggest that JE may reflect synovial inflammation of the TMJ.

Proinflammatory cytokines in temporomandibular joint synovial fluid before and after arthrocentesis.

OBJECTIVE: The aim of this study was to evaluate the levels of interleukin (IL)-1beta, IL-6, IL-8, IL-11, and tumor necrosis factor (TNF)-alpha in temporomandibular joint (TMJ) synovial fluid of the patients with internal derangement before and 2 weeks after arthrocentesis. STUDY DESIGN: Forty TMJs of 35 patients (29 females and 6 males, mean age 22.9 years) were included to the study. TMJs were divided into 2 groups: disc displacement with reduction (Group 1, n = 24) and disc displacement without reduction (Group 2, n = 16). Synovial fluid samples were obtained before and 2 weeks after arthrocentesis. IL-1beta, IL-6, IL-8, IL-11, and TNF-alpha concentrations were measured by using specific kits. RESULTS: Two weeks after the arthrocentesis procedures, all cytokines were found to be significantly decreased (P < .05) both in Group 1 and Group 2. The difference between 2 groups was insignificant (P > .05). CONCLUSION: Arthrocentesis is an effective technique for eliminating the studied cytokines from the TMJ synovial fluid.

Reactive arthritis and internal derangement of the temporomandibular joint.

OBJECTIVE: The objective of this study was to determine if temporomandibular joint (TMJ) samples positive for Chlamydia trachomatis have a greater presence of tumor necrosis factor-alpha (TNFalpha) or interleukin-6 (IL-6) when compared with Chlamydia-negative samples. STUDY DESIGN: Posterior bilaminar tissue samples removed during TMJ surgery from 70 patients were evaluated. Cryosections were stained using monoclonal antibody that identifies C. trachomatis. The presence of IL-6 and TNFalpha were evaluated by immunostaining in 15 samples positive and in 25 samples negative for the presence of C. trachomatis. RESULTS: Of the 70 TMJ samples, 32 (46%) were positive for C. trachomatis. In 15 samples positive for C. trachomatis, 10 (67%) were positive for TNFalpha and 7 (47%) for IL-6. In 25 samples negative for C. trachomatis, only 4 (16%) were positive for TNFalpha and only 2 (8%) for IL-6. Differences in C. trachomatis-positive samples versus negative were significant for both TNFalpha (P < .002) and IL-6 (P < .008). CONCLUSION: The presence of C. trachomatis in the TMJ is associated with a significantly increased presence of TNFalpha and IL-6.

Tumor necrosis factor-alpha increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint.

BACKGROUND: Synovitis, which is characterized by infiltration of inflammatory cells, often accompanies progression of clinical symptoms of the temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to play important roles in progression of synovitis. The purpose of this study was to examine production and gene expression of chemokines by synovial fibroblasts stimulated by tumor necrosis factor-alpha (TNF-alpha). METHODS: Protein levels of chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of chemokines was analyzed by real-time polymerase chain reaction (PCR). RESULTS: Production of interleukin (IL)-8, growth-related oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-1alpha and -1beta were not detectable in conditioned media of synovial fibroblasts, with or without TNF-alpha treatment. Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to TNF-alpha treatment were detected. CONCLUSIONS: Increased protein production and gene expression of chemokines by synovial fibroblasts in response to TNF-alpha treatment appears to play an important role in recruitment of inflammatory cells into synovium and the progression of synovitis in the TMJ.

Interleukin-6 family of cytokines as biochemical markers of osseous changes in the temporomandibular joint disorders.

The aim of this study was to find out whether there was a correlationship between the concentrations of interleukin-6 (IL-6), IL-11, and IL-17 in synovial fluid and osseous changes in the condyle. The synovial fluid was obtained from 61 patients with temporomandibular joint disorders (TMD) and seven healthy volunteers (controls). The concentrations of IL-6, IL-11, and IL-17 were measured by enzyme-linked immunosorbent assay. IL-6 was detected in 43 of 59 (73%), IL-11 in 23 of 52 (44%) and IL-17 in 14 of 51 (27%) samples of synovial fluid. The concentrations of IL-6 and IL-11 in the joints with osseous changes in the condyle were significantly higher than in the joints without osseous changes (P < 0.05) and also higher than in the joints of the control group (P < 0.05). In addition, there was a correlation of concentrations between IL-6 and IL-11 (P < 0.05). These results suggest that IL-6 and IL-11 may participate in the pathogenesis of TMD and induce osseous changes in the condyle.

Comparison of cytokine level in synovial fluid between successful and unsuccessful cases in arthrocentesis of the temporomandibular joint.

PURPOSE: The aim of this study was to compare proinflammatory cytokine levels between successful cases and unsuccessful cases of arthrocentesis in patients with internal derangement of the temporomandibular joint (TMJ). PATIENTS AND METHODS: This study involved 73 joints judged as successful and 30 judged as unsuccessful of 103 joints in 100 patients diagnosed with internal derangement of the TMJ and who underwent arthrocentesis. The diluted synovial fluid before undergoing arthrocentesis was aspirated from the superior joint space. The concentrations of interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, and IL-8 were measured using an enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each cytokine between successful cases and unsuccessful cases were analyzed statistically. RESULTS: There was a statistically significant difference between successful cases (72.2%) and unsuccessful cases (95.5%) in the detection ratio of IL-6 (P <.05). There was a statistically significant difference between successful cases (0.017 pg/100 microg protein) and unsuccessful cases (0.046 pg/100 microg protein) in the concentration of IL-1beta (P <.05). CONCLUSION: It has been shown that the presence of IL-1beta and IL-6 in synovial fluid may be indicators of possible unsuccessful treatment following arthrocentesis for internal derangement of the TMJ.

Expression of interleukin 6 in synovial tissues in patients with internal derangement of the temporomandibular joint.

Using an immunohistochemical technique, we examined synovial tissue from 46 temporomandibular joints (TMJ) with internal derangement in 44 patients. As controls, we examined synovial tissue specimens from 7 joints with habitual dislocation without pain. In synovial tissues from 21 of the 46 joints with internal derangement, interleukin 6 (IL-6) was expressed in the synovial lining cells and in the mononuclear cells infiltrating the periphery of the blood vessels. The density of IL-6-stained cells in specimens with internal derangement correlated significantly with the grade of joint effusion shown by magnetic resonance imaging (P=0.01, r=0.32).

Analysis of human leukocyte antigens in patients with internal derangement of the temporomandibular joint.

PURPOSE: Spondyloarthropathy includes the subcategory of reactive arthritis (ReA). Spondyloarthropathies are commonly associated with certain human leukocyte antigen (HLA) alleles. Because we identified bacteria associated with ReA within the temporomandibular joint (TMJ), we now evaluate the frequency of HLA alleles in patients with TMJ pathology. PATIENTS AND METHODS: HLA typing of 129 patients (121 females and 8 males) performed by standard microcytotoxicity technique. Thirty patients had only class I (HLA-A and -B loci) evaluated. Ninety-nine patients had both class I and class II (HLA-DR loci) evaluated. Identification of alleles at the C locus was not performed. The antigenic frequency in the study group was compared to US white control subjects using a 2-tailed Fisher's exact test with a Bonferroni multiple comparison adjustment. RESULTS: The following class I HLA alleles, -A1 (32%), -A2 (50%), -A3 (33%), -B7 (23%), -B14 (14%), -B35 (20%), and -B44 (36%), including the B7 cross-reactive group (CREG) (49%) and class II alleles -DR1 (25%) and -DR4 (34%), were found to have an increased frequency in our patient group. CONCLUSIONS: Our study shows an increased frequency of several alleles that have been previously associated with arthropathy, and the alleles of the B7 CREG, in patients with TMJ pathology. Patients with these alleles may have an increased risk for the development of internal derangement of the TMJ as a consequence of the bacterial/infectious agents and host interactions with the subsequent cytokine/inflammatory response being influenced by their HLA phenotype.

Tumor necrosis factor-alpha as a biochemical marker of pain and outcome in temporomandibular joints with internal derangements.

OBJECTIVE: Previous studies have demonstrated the presence of tumor necrosis factor-alpha (TNF) in human temporomandibular joint (TMJ) synovial fluid. The present study continues the investigation of the role of TNF in TMJs with internal derangements. MATERIALS AND METHODS: Synovial fluid was obtained from 18 TMJs in 12 patients undergoing either arthroscopy (14 joints) or arthrotomy (four joints) for internal derangements. Standardized clinical data were collected preoperatively, intraoperatively, and postoperatively. RESULTS: When pain on palpation was absent, the mean preoperative TNF level was 14 +/- 6 ng/mL. When pain on palpation was present, the mean TNF level was 42 +/- 39 ng/mL (significant difference at P = .05). When the surgical outcome was poor, the mean preoperative TNF level was 26 +/- 9 ng/mL. When the outcome was within the stated guidelines for a favorable result, the mean TNF level was 12 +/- 7 ng/mL (significant difference at P = .05). In addition, a significant reduction (P = .05) in TNF following joint lavage (preoperative, 48 ng/mL to postoperative, 7 ng/mL) was found. CONCLUSIONS: The finding of a positive correlation between preoperative pain and TNF values suggests a biochemical basis for the origin of the pain associated with internal derangements. The relationship between preoperative TNF levels and surgical outcome suggests that the prognosis for surgery may be predicted by measuring biochemical markers of joint disease.

A subluxing arthropathy associated with the anti-Jo-1 antibody in polymyositis/dermatomyositis.

Of 180 patients with polymyositis/dermatomyositis (PM/DM) seen at the University of Pittsburgh and affiliated hospitals since 1975, 21 of 100 tested positive for the anti-Jo-1 antibody. Sixteen of the 21 patients were women and 18 were white. Fifteen had adult PM, 4 had myositis in overlap with scleroderma, and 2 had adult DM. Evidence of interstitial lung disease was found in 12 of 18 anti-Jo-1 positive patients (67%), but in only 15 of 79 anti-Jo-1 negative patients (19%) (P less than 0.0002). The 21 anti-Jo-1 positive patients were divided into 3 separate groups based on the observed articular findings. Four patients had a deforming, predominantly nonerosive arthropathy with subluxations of the distal interphalangeal joints, especially the thumbs. Eight patients had a nondeforming arthropathy primarily affecting the small joints of the hands, wrists, shoulders, and knees. Those with deformities had a longer duration of arthritis compared with those with nondeforming arthropathy (mean 14.5 years versus 3.3 years). Nine anti-Jo-1 positive patients had no joint arthropathy. Three of 4 patients with deformities have required articular reconstructive surgery for subluxation, with 2 having associated subcutaneous calcinosis.

Identification of prostaglandin E2 and leukotriene B4 in the synovial fluid of painful, dysfunctional temporomandibular joints.

It has been hypothesized that prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) should be present in the synovial fluid of inflamed, dysfunctional temporomandibular joints. An assay to identify PGE2 and LTB4 and platelet-activating factor (PAF) was used, and a strong correlation between the levels of these lipid mediators of pain and inflammation and an index of clinical joint pathology was found.

[Antibodies against staphylococci in patients of a department for orthopedic surgery (author's transl)]. / Staphylokokken-Antikörper-Titer bei unfallchirurgischen Patienten. I. Mitteilung.

Sera from different groups of patients in a department of traumatic surgery were examined for staphylococcal alpha-antitoxin-titres. In comparison to a group of normal controls the following changes were found: 1. Patients, had significantly raised titres, if they had undergone surgery because of closed fractures, pseudarthrosis and luxations and even if the postoperative course was uneventful. This can be explained through the wide-spread occurrence of staphylococci in hospitals, which can invade the organisms through an incision, the skin or mucous membranes. These findings should be kept in mind while estimating staphylococcal antitoxin-titres in patients hospitalized over a long period. 2. Patients suffering from surgical infections and also paraplegics showed still more significantly raised antitoxin-titres in comparison to the normal controls or to patients, who had undergone aseptic surgery. Increased titres were found even in the sera of patients, whose wounds did not drain staphylococcus aureus. Patients suffering from chronic staphylococcal osteomyelitis showed the highest mean values of antitoxin-titres; these patients, however, had also the greatest variations with high and low levels. The question arouse whether a high or a low level corresponds to the severity of the disease. It was found that it is necessary to titrate different antibodies against staphylococcal toxins. In a second paper the results of the simultaneous determination of alpha-antitoxin and anti-PV-leucocidin in patients with posttraumatic bone infections will be presented.