Annelise Küseler

Intra-articular steroid injection for temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic review on efficacy and safety

OBJECTIVE To determine the current level of evidence for the use of intra-articular corticosteroid injections (IACI) against temporomandibular joint (TMJ) arthritis in patients with juvenile idiopathic arthritis (JIA) with a particular focus on clinical and radiological improvements and safety profile. METHODS A comprehensive electronic search strategy was performed in all major medical databases in February 2012. Studies were selected independently by two reviewers in accordance with a pre-specified protocol and a risk of bias assessment for all included studies. RESULTS Ninety-four unique citations were identified of which seven remained after the inclusion criteria were applied and all of these were assessed to have a high risk of bias. The current limited level of evidence suggests potential beneficial properties of IACI in patients with TMJ arthritis-related symptoms and/or MRI-verified signs of TMJ inflammation. Currently, no scientific evidence substantiates the effect of IACI in terms of (I) improving maximal mouth opening capacity significantly, (II) reducing radiological disease progression, (III) normalising/improving mandibular growth, and (IV) increasing efficacy upon repeated injections. CONCLUSION The current level of evidence allows only very limited conclusions on the effect of IACI therapy in patients with TMJ arthritis. Knowledge on the long-term impact of IACI on mandibular growth is not available. Future studies designed in accordance with evidence-based standards are needed to allow a more general conclusion on efficacy and safety of this treatment modality in patients with TMJ arthritis.

Reduced mandibular growth in experimental arthritis in the temporomandibular joint treated with intra-articular corticosteroid

The aim of this investigation was to study the effect of intra-articular (i.a.) corticosteroid injections (IACIs) in the temporomandibular joint (TMJ) on mandibular development in antigen-induced TMJ arthritis. Ten-week-old female New Zealand white rabbits (n = 42) were randomly divided into four groups: group A, control (no injections); group B, placebo (repeated i.a. TMJ saline injections); group C, untreated arthritis (repeated induction of TMJ arthritis); and group D, steroid (repeated induction of TMJ arthritis + IACI). All animals had two tantalum implants inserted in the right side of the mandible serving as stable landmarks for later growth analysis. One implant was inserted close to the symphysis and one in the molar region. Computerized tomographic (CT) full-head scans were carried out at 14 (T1) and 26 (T2) weeks of age. (Dropout of animals at T2; group C, n = 7, and group D, n = 3.) Absolute and relative intra- and inter-group growth variations were evaluated during the growth period by comparison of CT scans. One-way analysis of variance was used for T1 statistical analysis, and absolute intra-group and relative inter-group growth differences between T1 and T2 were evaluated by Students t-tests. At T2, the animals in the group A had greater sagittal and vertical mandibular growth compared with the other three groups. TMJ arthritis caused diminished mandibular growth. However, relative mandibular growth was significantly less in group D. The findings of this study do not indicate a positive long-term effect in the use of IACI in the TMJ as an early treatment intervention against TMJ inflammation in growing individuals.

Orthopaedic splint treatment can reduce mandibular asymmetry caused by unilateral temporomandibular involvement in juvenile idiopathic arthritis.

Unilateral temporomandibular joint (TMJ) arthritis in juvenile idiopathic arthritis (JIA) patients often induces asymmetric dentofacial growth. This study evaluates the effects of an orthopaedic functional appliance worn full time to reduce asymmetric mandibular growth in JIA patients. Twenty-two JIA patients with unilateral TMJ involvement were included in the study (mean age 7.5 years, range: 3.8-13.8 years). They all received orthopaedic treatment with a functional appliance, a so-called distraction splint (mean treatment time 57 months). Panoramic tomograms or cone beam-computerized tomograms were taken before and within 12 months after treatment cessation. At both time points, the ratio between the healthy and the affected side of the mandible was evaluated in terms of inter-side differences in condylar height, ramus height, and total vertical mandibular height. Orthopaedic functional treatment reduced mandibular asymmetries in terms of ramus height and total vertical mandibular height (P < 0.05). Mandibular growth rates in the affected and the non-affected sides were comparable in most patients. Our study finds evidence to support that a distraction splint can normalize mandibular vertical growth in the affected side. We therefore suggest implementation of distraction splint therapy in the treatment of JIA patients with unilateral TMJ arthritis.

Quantitative histological changes of repeated antigen-induced arthritis in the temporomandibular joints of rabbits treated with intra-articular corticosteroid

BACKGROUND To compare the inflammatory changes of antigen-induced temporomandibular joint (TMJ) arthritis in rabbits by different histological methods and to evaluate the immunomodulatory effect of intra-articular corticosteroid injections histologically. METHODS 35 rabbits (10 weeks old) pre-sensibilized with ovalbumin were divided into three groups: a placebo group of five (saline), an arthritis group of 15 (ovalbumin) and a steroid-treated group of 15 (ovalbumin + corticosteroid). Additionally, a group of seven rabbits receiving no sensibilization with ovalbumin and no intra-articular injections served as controls. Histomorphometry of the inflammatory changes in the subsynovial connective tissue (SSCT) of the TMJ included: (i) semi-quantitative (S-Q) scoring of inflammation and synovial proliferation, (ii) thickness measurements and fractional surface and (iii) stereological quantitative assessment of volume and plasma cells in thick sections of the SSCT by an optical fractionator. RESULTS The histomorphometry showed synovial proliferation in both the arthritis and the steroid groups. The plasma cell count obtained by the optical fractionator was significantly reduced when treating the TMJ with corticosteroids. However, the thickness of the synovial lining and volume of the SSCT as well as S-Q scoring of inflammation showed no difference between the arthritis and the steroid-treated groups. The optical fractionator proved a superior tool compared to S-Q assessments. CONCLUSION Counting of plasma cells in the SSCT showed that corticosteroids reduced the inflammation, but did not eliminate it. Semiquantitative scoring of synovial proliferation and inflammation demonstrated low sensitivity regarding changes in immunomodulation in antigen-induced arthritis compared to stereological quantitative estimations using an optical fractionator.

Orofacial Symptoms Related to Temporomandibular Joint Arthritis in Juvenile Idiopathic Arthritis: Smallest Detectable Difference in Self-reported Pain Intensity

Objective. Temporomandibular joint (TMJ) inflammation in patients with juvenile idiopathic arthritis (JIA) may lead to mandibular growth disturbances and interfere with optimal joint and muscle function. Orofacial symptoms are common clinical findings in relation to TMJ arthritis in adolescence. Knowledge about their clinical manifestation is important for TMJ arthritis diagnosis, treatment choice, and outcome evaluation. The aim of our prospective observational study was to evaluate and describe the frequency, the main complaints, and the localization of TMJ arthritis-related orofacial symptoms. The smallest detectable differences (SDD) for minimal, average, and maximal pain were estimated. Methods. Thirty-three patients with JIA and arthritis-related orofacial symptoms in relation to 55 affected TMJ were included in our questionnaire study (mean age 14.11 yrs). Calculation of the SDD was based on a duplicate assessment 45 min after the first questionnaire was completed. Results. The majority of the patients had common orofacial symptoms during mastication and maximal mouth opening procedures. Persistent orofacial symptoms were rare. The TMJ area in combination with the masseter muscle region was the orofacial region where symptoms were most common. The SDD for minimal, average, and maximal pain were between 10 and 14 mm on a visual analog scale. Conclusion. Our study offers new knowledge about TMJ arthritis-related orofacial symptoms that may aid diagnosis and clinical decision-making. We suggest that TMJ arthritis-related orofacial symptoms could be understood as products of the primary TMJ inflammation in combination with secondary myogenic and functional issues.

Smallest detectable differences in clinical functional temporomandibular joint examination variables in juvenile idiopathic arthritis

OBJECTIVE Temporomandibular joint (TMJ) arthritis in juvenile patients may interfere with optimal joint function and mouth opening patterns. Clinical assessment of maximal mouth opening capacity, laterotrusion and protrusion is critical to TMJ arthritis diagnosis, treatment choice and evaluation of a therapeutic intervention. The aim of the study was to determine the smallest minimal threshold at which differences in maximal mouth opening capacity, laterotrusion, and protrusion between two consecutive observations can be determined. SETTING AND SAMPLE POPULATION Department of Orthodontics, University of Aarhus, Denmark. Forty-two consecutive patients with juvenile idiopathic arthritis. MATERIAL AND METHODS Two experienced dentists used a calibrated metallic ruler to measure maximal mouth opening capacity, laterotrusion, and protrusion. Each measurement was carried out thrice by each observer. Intra- and inter-observer variation and the smallest detectable difference were calculated for each variable. RESULTS The smallest detectable differences were as follows: maximal mouth opening capacity 4.9 mm, laterotrusion 2.4 mm, and protrusion 2.8 mm (one observer and one measurement). These differences declined when measurements were repeated; maximal mouth opening capacity 3.3 mm, laterotrusion 1.4 mm, and protrusion 1.8 mm (two observers with three measurements each). We found no support for a relationship between measurement variation and patient age, measurement variation and TMJ pain, or between measurement variation and previous/current TMJ arthritis. CONCLUSION The importance of the implementation of a standardized measurement protocol is emphasized including repeated measurements to reduce the smallest detectable difference.

Intra-articular vs. systemic administration of etanercept in antigen-induced arthritis in the temporomandibular joint. Part II: mandibular growth

BackgroundTemporomandibular joint (TMJ) arthritis in children causes alterations in the craniomandibular growth. Resultant abnormalities include; condylar erosions, a posterior mandibular rotation pattern, micrognathia, malocclusion with an anterior open bite, altered joint and muscular function occasionally associated with pain. These alterations may be prevented by early aggressive anti-inflammatory intervention. Previously, we have shown that intra-articular (IA) corticosteroid reduces TMJ inflammation but causes additional mandibular growth inhibition in young rabbits. Local blockage of TNF-α may be an alternative treatment approach against TMJ involvement in juvenile idiopathic arthritis (JIA). We evaluated the anti-inflammatory effect of IA etanercept compared to subcutaneous etanercept in antigen-induced TMJ-arthritis in young rabbits in terms of mandibular growth. This article (Part II) presents the data and discussion on the effects on facial growth. In Part I the anti-inflammatory effects of systemic and IA etanercept administration are discussed.MethodsArthritis was induced and maintained in the TMJs of 10-week old pre-sensitized rabbits (n = 42) by four repeated IA TMJ injections with ovalbumin, over a 12-week period. One group was treated weekly with systemic etanercept (0.8 mg/kg) (n = 14), another group (n = 14) received IA etanercept (0.1 mg/kg) bilaterally one week after induction of arthritis and one group (n = 14) served as an untreated arthritis group receiving IA TMJ saline injections. Head computerized tomographic scans were done before arthritis was induced and at the end of the study. Three small tantalum implants were inserted into the mandible, serving as stable landmarks for the super-impositions. Nineteen variables were evaluated in a mandibular growth analysis for inter-group differences. All data was evaluated blindedly. ANOVA and T-tests were applied for statistical evaluation using p < 0.05 as significance level.ResultsSignificant larger mandibular growth disturbances were observed in the group receiving IA saline injections compared with the systemic etanercept group. The most pronounced unfavourable posterior mandibular rotation pattern was observed in the group receiving IA saline injections.ConclusionIntervention with systemic etanercept monotherapy equivalent to the recommended human dose allows a mandibular growth towards an original morphology in experimental TMJ arthritis. Systemic administrations of etanercept are superior to IA TMJ administration of etanercept in maintaining mandibular vertical growth.

Association between condylar morphology and changes in bony microstructure and sub-synovial inflammation in experimental temporomandibular joint arthritis.

BACKGROUND In juvenile idiopathic arthritis involvement of the temporomandibular joints (TMJs) is often associated with mandibular growth deviations. The relation between the growth deviations and severity of the inflammation, condylar shape, the micro-architecture, and the quality of the bone has not previously been investigated. This paper studies the effect on the bony structures in mandibular condylar development in rabbits with antigen-induced arthritis. METHODS Included were 42 juvenile rabbits with ovalbumin-induced arthritis of the TMJs treated with intraarticular saline, intraarticular etanercept or subcutaneous etanercept. A TMJ from each animal was scanned using micro-computed tomography and structural parameters were calculated. Three-dimensional reconstructions of the mandibular condyle were scored blindly as normal or abnormal. TMJs were stratified for condylar morphology and were evaluated against data on trabecular structural parameters, inflammation, degree of mineralization, overall mandibular growth, and mineral apposition rate. RESULTS Abnormal morphology were seen in 15/32 animals available for data analysis. Erosions were an uncommon finding. Abnormal morphology was strongly related to the degree of inflammation. The trabecular separation was larger in group with abnormal morphology than in the group with normal morphology. Abnormal condylar morphology was not associated with overall mandibular growth. No differences were observed in mineral apposition rate. No differences in structural parameters were seen according to treatment modality. CONCLUSION We showed that severe inflammation in the TMJs during mandibular development was associated with morphological changes in the mandibular condyle. These changes were predominantly seen at the macro-morphological level and only very few differences were structural.

Clinical predictors of temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic literature review

AIM To assess the level of evidence for subjective and objective parameters in clinical orofacial examination and determine if predictors for temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA) patients exist in the current literature. METHOD A comprehensive systematic electronic search strategy was performed in all major medical databases in June 2015. Studies were selected independently by two reviewers in accordance with a prespecified protocol and a risk of bias assessment for all included studies. Subjective examination outcome measures assessed were pain, decreased TMJ function, and TMJ sounds. The objective outcome measures assessed were maximal incisor opening, mandibular asymmetric opening, condylar translation, protrusion, myofascial pain on palpation, facial asymmetry, and micro- or retrognathism. RESULTS The electronic database search identified 345 unique citations. After application of our strict, predefined inclusion and exclusion criteria, 21 articles were included and data extracted. The study heterogeneity did not allow for meta-analyses. No singular outcome measure can be suggested as a predictor of TMJ involvement in JIA, as sensitivity and/or specificity is too low compared to contrast-enhanced magnetic resonance imaging. CONCLUSION The current low level of evidence and study heterogeneity do not allow us to conclude on singular clinical outcome measures. To increase study comparability, we call for a standardized terminology and evidence-based guidelines for clinical orofacial examination parameters in JIA patients.

A Novel Semiautomatic Technique for Volumetric Assessment of the Alveolar Bone Defect Using Cone Beam Computed Tomography

Objective The aims of this study were (1) to determine the three-dimensional anatomical boundaries of the alveolar bone defect in cleft lip and palate (CLP) patients, (2) to precisely translate these anatomical boundaries into reliable cephalometric landmarks and planes that can be used for cone beam computed tomography (CBCT) analysis, (3) to standardize image acquisition and reconstruction parameters, and (4) to test the reproducibility of the proposed protocol for measuring the predefined alveolar bone defect, using a third-party software. Methods The alveolar bone defect volume of 10 randomly selected patients with unilateral CLP (UCLP) aged 8 years and 6 months to 11 years and 2 months was evaluated on preoperative and 1-year postoperative CBCT scans using a semiautomatic, standardized protocol. The alveolar bone graft outcome was calculated as a percentage of the bone fill using the formula (VOLpre – VOLpost)/VOLpre) × 100. Intra- and interobserver reliability was assessed. Results Intra- and interobserver reproducibility was excellent for volumes and bone fill as no statistically significant difference (P < .001) was seen between the different sets of measurements, and Pearson correlation coefficients were large (intraobserver: r > .9849, interobserver: r > .8784). The Bland-Altman plots indicated that the differences between the plots were not patterned. Conclusions Volume determination using CBCT, third-party medical image processing software, and the presently defined image acquisition and reconstruction parameters, including anatomical boundaries, is a reproducible and practical method for assessing the volumetric outcome of secondary alveolar bone grafting in patients with UCLP.