The impact of temporomandibular joint arthritis on functional disability and global health in patients with juvenile idiopathic arthritis

The impact of temporomandibular joint arthritis on functional disability and global health in... Summary Objectives The objective of the study was to evaluate the impact of temporomandibular joint (TMJ) arthritis on the functional disability and quality of life in patients affected by juvenile idiopathic arthritis (JIA). Materials and Methods Sixty-two consecutive patients with JIA with or without TMJ arthritis and 35 healthy control subjects were enrolled in the study. The demographic data, disease activity and clinical characteristics were obtained from all patients. The functional disability was assessed using the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ). The oral health-related quality of life (OHRQoL) was assessed using the Child Perception Questionnaire (CPQ11-14). Possible determining factors of TMJ arthritis comprised demographic, disease characteristics and scores derived from questionnaires that were assessed by a uni and multivariable logistic regression analysis. Results Compared with patients without TMJs arthritis, JIA patients with TMJ arthritis presented higher functional disability. The multivariable logistic regression analysis performed showed that female subjects (OR = 1.5, P = 0.041), with a JIA duration over 3.9 years (OR = 2.7, P = 0.033) and presenting higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis. Conclusions JIA patients with TMJ arthritis presented higher functional disability and lower OHRQoL scores compared with JIA patients without TMJ arthritis. TMJ arthritis was strongly associated with JIA duration and activity, especially in female patients. Introduction Juvenile idiopathic arthritis (JIA) is a chronic disease of unknown ethiology, with an estimated incidence of 16 to 150 cases per 100000 children worldwide, characterized by chronic synovitis in one or many joints and represents an important cause of disability in childhood (1). Temporomandibular joint (TMJ) arthritis is a common consequence of the systemic disease in patients with JIA (2,3). Previous reports have shown that up to 93% of patients with JIA may present early inflammatory findings in TMJs (4,5). During JIA, the impairment due to TMJ arthritis may lead to difficulties in many daily activities, such as eating, smiling and performing oral hygiene (6). The appearance of TMJ arthritis in JIA patients was shown to perhaps also determine, if not properly treated, a reduced and asymmetric craniofacial growth with the appearance of skeletal malocclusions and micrognathia (7–9). In JIA patients, the appearance of TMJ arthritis during childhood has been demonstrated to determine a high percentage of TMJ and orofacial disorders up to 26 years from JIA disease onset (10,11). The diagnosis of TMJ arthritis in JIA patients during the active phases of the disease is a challenging task. In fact, previous reports showed that pain, one of the main factors associated with TMJ arthritis, is a very unreliable sign of disease because it is reported in only a quarter of JIA patients with the presence of manifest radiological signs of TMJ arthritis (2,12). However, the presence of TMJ involvement during JIA has been demonstrated to influence the quality of life of JIA patients (13) and to be a significant burden on patient’s caregivers (14). Due to the involvement of TMJs, orofacial pain is a frequent finding during JIA and is reported to severely affect daily life in almost 25% of cases (15). For many years, several health-related quality of life (HRQoL) questionnaires have been developed to detect the global impact of JIA on the daily quality of life and the patient-relevant burden of patients affected by JIA (16,17). During the last few decades, the Child Oral Health Quality of Life Instrument (COHQOL) (18), the Child Oral Impact on Daily Performances (Child-OIDP) (19), the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module 3.0, the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), the Paediatric Rheumatology Quality of Life Scale (PRQL), and the Childhood Arthritis Health Profile (CAHP) (20) have been used to measure the health status and the subjective burden of disease during JIA. However, an advanced generation of questionnaires has been developed to more appropriately assess the global functional disability and daily functions in children, such as the Childhood Health Assessment Questionnaire (C-HAQ) and the Child Perception Questionnaire (CPQ11-14), both of them translated into many different languages (21). C-HAQ and CPQ11-14, with its disease-specific sections, have been validated to estimate functional assessment during JIA (22). C-HAQ has been shown to specifically determine a child’s ability to perform different daily functions at disease onset during JIA, such as dressing, grooming, arising, eating, walking, hygiene, reach and grip (2,22). However, in order to better understand the impact that certain oral conditions cause on the overall quality of life, CPQ11–14 has been developed with the main purpose of assessing the oral HRQoL (OHRQoL) in children and adolescents by four domains: oral symptoms, functional limitations, emotional and social well-being (23,24). As a negative impact of arthritis in TMJs during JIA, there is an increasing interest concerning the impact that TMJ arthritis exerts on the HRQoL in JIA patients. In light of these findings, the aim of this study was to assess the impact induced by TMJ arthritis on functional disability and OHRQoL in a cohort of patients affected by JIA with or without TMJ arthritis compared with healthy subjects and to determine what the greatest determining factors of TMJ arthritis were. The null hypothesis to invalidate was that JIA patients with and without TMJ arthritis presented no differences in clinical characteristics, functional disability and OHRQoL. Materials and methods Study design Patients with a diagnosis of JIA performed in accordance with ILAR criteria (25), with and without TMJ arthritis were enrolled in the present case–control study between February 2012 and September 2017. The ethical committee of the University of Messina approved the protocol of the study (#918-10, 5 February 2010). The study was registered at clinicaltrials.gov (ID: NCT03008681). The written informed consent was acquired from the parents of each patient who were informed about the study type and characteristics, in accordance with the Declaration of Helsinki in 1975, revised in 2000. The inclusion criteria were: 1. diagnosis of JIA (only in JIA groups) and 2. no injections of any steroid on TMJ during the last 12 months. The exclusion criteria were: 1. previous orthodontic treatment, 2 previous maxillofacial surgery and 3. genetic or congenital syndromes or any concurrent medical condition that could influence the results of the study. Seventy-two consecutive patients with a diagnosis of JIA aged between 8 and 17 years (38 female and 34 males, mean age of 11.2 ± 2.2 years) were initially enrolled as the study group. Thirty-five healthy subjects chosen from all patients attending dental clinics for routine oral visits, who were matched for age and sex (17 female and 18 males, mean age of 11.9 ± 2.2 years), were enrolled as the control group. The healthy subjects did not have any history of rheumatic, congenital or systemic diseases or TMJ disorders and presented a good occlusion and maxillary relationship. After the first screening, 10 patients with JIA were excluded because they did not fully meet the inclusion criteria (n = 4), declined to participate (n = 2) or missed the clinical examination (n = 4). Thus, the final number of patients assessed for eligibility as the JIA group was 62. Data collection The clinical characteristics data and subtype of JIA was obtained from the hospital chart of each patient and was documented by a paediatric rheumatologist (Table 1). Table 1. Sociodemographic and clinical characteristics of the study population. Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Values are expressed with mean (±SD). View Large Table 1. Sociodemographic and clinical characteristics of the study population. Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Values are expressed with mean (±SD). View Large The clinical and orthodontic assessment was performed in all patients by the same examiner who was not involved in the subsequent data analysis. The assessment comprised a full mouth evaluation and the valuation of TMJ by recording, in each patient, clicking, crepitus, anterior translation, pain with palpation and opening, symmetry during opening, capability of protrusion and laterotrusion and the maximum mouth opening. The mouth opening was measured by the Therabite Measuring Scale (Atos Medical, Milwaukee, WI), determining the differences from normal values of children up to 18 years (26). In all enrolled subjects, TMJs were evaluated by Magnetic Resonance Imaging (MRI) scans. All patients underwent Gadolinium-enhanced MRI. The MRI evaluation included coronal T1- and T2-weighted images, sagittal T1-weighted and dual-echo T2-weighted images, and, following the intravenous administration of Gadolinium contrast material, sagittal and coronal fat-saturated T1-weighted images. Axial and coronal T2 were acquired perpendicular to the mandibular condyle and parallel to the ramus of the mandible. Sagittal oblique images were acquired with 2-mm slices and a 12-cm field of view and 256 × 224 matrix. Any clinical or radiological signs at MRI of TMJ arthritis with active findings of synovitis, effusion or pannus and MRI signs of joint structural damage such as flattening of the mandibular head, flattening of the fossa and the presence of bone marrow edema, erosions or osteophytes were recorded during the first clinical and MRI examination. The study involved three groups (Table 1): group of JIA patients with TMJ arthritis (JIA+TMJ arthritis group), group of JIA patients without TMJ arthritis (JIA group) and healthy subjects group (control group). During the calibration sessions and after a clinical evaluation, intra-examiner repeatability and reproducibility was evaluated to obtain duplicate measurements of clinical parameters from patients randomly selected from the sample. One examiner evaluated the parameters of the two JIA groups and a second examiner evaluated the control group. The intra-examiner agreement, which was 0.815 (95% CI = 0.73–0.9), was obtained by calculating Cohen’s k coefficient from all outcomes deriving from the two HRQoL questionnaires and predicted a good degree of reliability. Sample size The sample size was established considering the mean prevalence of JIA in the population equal to 0.08% (1), the study group incidence of 2.8% (as the prevalence of JIA in our database), an alpha level of 0.05 and a power of 80%. A minimum sample of 51 JIA patients was determined to ensure a good sample size. Sixty-two patients affected by JIA and 26 healthy subjects in the control group were finally enrolled. Functional disability and OHRQoL measurement In the enrolled patients, functional disability was assessed by the Italian version of the C-HAQ questionnaire (21). The C-HAQ consisted of several domains aimed at evaluating the impact of the frequency of functional disability and quality of care related to daily life activities and the ability of the patient to achieve distinct functions. The C-HAQ version chosen for this study was composed of seven different domains regarding daily activities like walking, eating, arising, dressing, hygiene, gripping and reaching/activity calculated by a range from 0 (no or minimal physical disability) to 3 (very severe physical disability). To measure the parent’s global assessment of the general health of a child’s in the last 10 days a Visual Analog Scale (PRgloVAS) [0–10-cm, ranged from 0 (very health) to 10 (the poorest)] was chosen. Given the absence of a questionnaire to specifically assess the OHRQoL in JIA patients with TMJ arthritis, in the present study, we decided to adopt the Child Perception Questionnaire (CPQ11-14), which was already validated for children with TMJ disorders (18). The version of CPQ11-14, chosen for this study, comprised four health domains (oral symptoms, functional limitations, social well-being and emotional well-being) aimed at specifically measuring the impact of oral disease and the extent to which the patient’s condition affected his/her overall global well-being in the previous 3 months. In the CPQ11-14, the answer options were ‘never = 0’; ‘once or twice = 1’; ‘sometimes = 2’; ‘often = 3’; ‘every day or almost every day = 4’. The summary score following the sum of these domains ranged from 0 to 140. A low total summary score of CPQ11-14 predicted a good OHRQoL, whereas a high summary score predicted a low OHRQoL. Both questionnaires were filled out by the patient aged >9 years old or by one of the caregivers. Statistical analysis All statistical analyses were executed using a software program (SPSS version 17.0 for Windows, Chicago, IL). The parametric approach was used because the data are normally distributed, as verified by the Kolmogorov–Smirnov test. The chi-square test and the t-test were used to compare the categorical and the continuous variables, respectively. A univariable logistic regression analysis was used to assess the influence of the quality of life measurements on TMJ involvement. The same analysis was performed in order to recognize factors distinguishing JIA patients with the presence/absence of TMJ arthritis by using the C-HAQ and CPQ11-14 domains as exploratory measures. To recognize factors independently associated with TMJ arthritis, multivariable logistic regression was performed. P < 0.05 was considered to be statistically significant. Results The demographic data, age and gender distribution, JIA types, drug therapy and the serological values of the sample are presented in Table 1. A total of 88 patients participated in the study; 32 patients in the JIA+TMJ group, 30 patients in the JIA group and 26 patients in the control group. The examined groups were matched for age and gender. One patient in the JIA+TMJ arthritis group and one patient in the JIA group were <9 years old. Regarding the JIA patients, JIA was diagnosed at 8.7 ± 3.1 (SD) years of age. Of the JIA patients, 35.7% presented JIA of up to 2 years of duration, 27.8% between 2 and 5 years of duration and 36.5% more than 5 years of duration. Nine patients in the JIA+TMJ group (28.1%) and seven (23.3%) in the JIA group presented rheumatoid-factor–negative polyarthritis (Table 1). Eighteen patients (56.2%) in the JIA+TMJ group and 15 patients (50%) in the JIA group underwent DMARD at least once while 18 patients (56.2%) in the JIA+TMJ group and 15 patients (30%) in the JIA group underwent biological drugs (Table 1). In the JIA+TMJ group, 19 patients (59.4%) presented bilateral and 13 (10.6%) patients unilateral TMJ arthritis, with the presence of a hypoplastic mandibular condyle that was found bilaterally in 18 (56.2%) and unilaterally in 14 (43.8%) patients. Pain in TMJs was present, only in 19 patients in the JIA+TMJ group (59.4%). Moreover, in the JIA+TMJ group, 23 (71.9%) patients presented myofascial pain, associated in 19 patients (59.4%) with a limitation of mouth opening. Even in the JIA+TMJ group, the mean maximum mouth opening was 34.2 ± 2.3 mm, whereas in the JIA and control groups the mean values were 40.7 ± 2.3 mm and 43.9 ± 1.8 mm, respectively (Table 1). In the JIA+TMJ group, at MRI, clear signs of TMJ involvement were present in 26 patients (81.2%), of which 21 were bilateral (65.6%) and 5 unilateral (15.6%) patients. Moreover, all patients in the JIA+TMJ group showed clear signs of active TMJ arthritis, which were mild in 19 patients (59.4%) and severe in 13 patients (40.7%). Moreover, 16 patients (50%) presented condylar deformities that were mild in 9 patients (28.1%) and severe in 8 patients (25%). Regarding the C-HAQ and the CPQ11-14, patients in the JIA+TMJ group showed statistically significant differences in the disability score compared with patients in the JIA and control groups (Figure 1 and 2). Figure 1. View largeDownload slide National version of the childhood health assessment questionnaire (C-HAQ) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 1. View largeDownload slide National version of the childhood health assessment questionnaire (C-HAQ) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 2. View largeDownload slide Child Perception Questionnaire (CPQ11-14) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 2. View largeDownload slide Child Perception Questionnaire (CPQ11-14) scores of the patient sample. Results are presented as mean and confidence intervals (CI). As reported in Figure 1, patients in the JIA+TMJ group presented a mean score of more than twice the C-HAQ with respect to the domains related to eating, hygiene and reaching activities, and the PRgloVAS score, both significantly higher compared with patients of the other groups. Moreover, compared with the control group, patients in the JIA group presented higher, but not significant, values of dressing, eating and reaching activities. Regarding the CPQ11-14, the patients in the JIA+TMJ group presented lower scores regarding the domains of functional limitations and well-being, whereas they presented higher scores in domains of oral symptoms compared with the other two groups. Moreover, as reported in Table 2, the univariate analyses (odds ratios [ORs] with 95% confidence intervals), which assessed the association of JIA activity/disability and quality of life with TMJ arthritis, showed that, in the JIA+TMJ group, a significant association was found between TMJ arthritis and the C-HAQ and CPQ11-14 domains. Disease activity and disability were higher in the patients in the JIA+TMJ group which presented higher values especially for eating (OR = 5.8, P = 0.015), hygiene (OR = 3.4, P = 0.028) and in the PRgloVAS score (OR = 3.6, P = 0.037). Regarding the CPQ11-14 domains, the JIA+TMJ group presented higher scores compared with the other two groups regarding oral symptoms and functional limitations (OR = 2.4, P = 0.013 and OR = 3.7, P = 0.021, respectively). Table 2. Univariable logistic regression analysis of the quality of life measurements of the patient sample. Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Values expressed OR (95% CI); ns, not significant. View Large Table 2. Univariable logistic regression analysis of the quality of life measurements of the patient sample. Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Values expressed OR (95% CI); ns, not significant. View Large In the final regression model, all variables significantly related to TMJ arthritis were selected, in the univariate analysis, based on OR such as gender, JIA duration, RF, number of active joints, ESR, C-HAQ and CPQ11-14 global scores. In order to validate also for the level of disease activity, in the final model, the score results were adjusted with the OR for the RF values and the number of active joints. The multivariable analysis demonstrated that variables such as the female gender (OR = 1.5, P = 0.041), JIA duration over 3.9 years (OR = 2.7, P = 0.033) and having higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis (Table 3). Table 3. Multivariable logistic regression analysis of quality of life measures, disease activity and clinical and demographic characteristics associated with TMJ involvement. Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns ns, not significant. View Large Table 3. Multivariable logistic regression analysis of quality of life measures, disease activity and clinical and demographic characteristics associated with TMJ involvement. Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns ns, not significant. View Large For the multivariate model, all the measures on the correct fit were calculated; adjusted R2 = 0.702, residuals degrees of freedom = 83; a significance level of the model P = 0.001, so we obtained satisfactory results that guarantee an adequate degree of fit to the data. Moreover, the non-significance of the Deviance test and the Pearson test (P = 0.950 and 0.991, respectively) leads to accepting the hypothesis that there are no significant differences between the observed values and the theoretical ones, deriving from the adopted model. Discussion The objective of this study was to evaluate the impact of TMJ arthritis and its determining factors on functional disability and OHRQoL in patients affected by JIA. The present study showed an association between JIA disease duration and activity and TMJ arthritis in patients affected by JIA. In our cohort, patients with JIA and TMJ arthritis presented more functional disability (assessed by C-HAQ) and lower OHRQoL (assessed by CPQ11-14) compared with JIA patients without TMJ arthritis and healthy subjects. Moreover, there was an independent strict association between TMJ arthritis and the duration of JIA <3.9 years, especially in female patients. In our sample, a high proportion of JIA patients presented TMJ involvement (52%). The diagnosis of TMJ arthritis was performed, in accordance with previous studies, by a combined clinical and MRI evaluation of TMJs that detected, more specifically, the presence of TMJ arthritis (4,27). The associations found in our study, between TMJ arthritis and JIA disease characteristics (70% in total), were in accordance with previous clinical and radiological studies (5,28) that reported signs of TMJ arthritis, in JIA patients, in a proportion from 40% to 85% (29). TMJ arthritis comprises a group of different signs and symptoms of dysfunctions in TMJs, including facial and muscular pain and click (30,31). However, even if it was reported as a frequent finding in JIA patients, TMJ arthritis, although present, in most of JIA patients is an asymptomatic disease, especially at a young age (2,12,32). Indeed, in our sample, a frequency of clinical pain in TMJs was observed in only 59.4% of JIA patients who, however, presented a high percentage of clear signs of TMJ arthritis at MRI (81.2%). In accordance with our results, previous studies demonstrated that clear signs of pain in TMJs, one of the better predictors of arthritis and joint destruction in TMJs, are usually reported in only 14–20% of patients in which clear radiological signs of TMJ arthritis are present (2,12). Moreover, this study showed that JIA patients with TMJ arthritis presented a significant higher functional disability and daily difficulties (high mean score of C-HAQ) compared with JIA patients without TMJ arthritis and to healthy subjects. In accordance with our results, previous reports demonstrated that TMJ arthritis and dysfunctions negatively influenced the daily functions and quality of life in JIA patients (17,22,33). JIA patients usually present severe articular symptoms, such as pain, joint contracture or large effusion, and a rapid clinical improvement that often ensues may have a relevant impact on their psychosocial health, leading to a detectable improvement in their emotional well-being, behavior or self-esteem (33,34). Moretti et al. (34) indicated that the C-HAQ questionnaire is a comprehensive tool that evaluates the physician’s global assessment of the disease and the relative responsiveness of condition-specific measures after intra-articular corticosteroid injection during JIA. Moreover, Ruperto et al. showed that the Italian versions of the C-HAQ/CHQ presented a reliable and valid tool to capture the functional, physical and psychosocial well-being of children with JIA (21). More specifically, Weiss et al. (2), in a cohort of children with a new-onset of JIA, found that JIA patients with TMJ dysfunction and orofacial symptoms presented low C-HAQ scores. In the study of Weiss et al. (2), the C-HAQ score was tested for the assessment of JIA disease activity and disability in JIA patients with MRI and ultrasound findings of TMJ arthritis. Moreover, Frid et al. (22), on a cross-sectional cohort of 3343 children with JIA also found that C-HAQ and PRgloVAS scores were useful tools to assess the functional disability in JIA patients with TMJ. In accordance with the results of our study, previous reports demonstrated that JIA patients showed a strong relationship between TMJ arthritis and high functional disability and low quality of life (2,6,11,12,15,35). Leksell et al. (15) demonstrated, in a clinical study, that almost 80% of JIA patients presented pain in TMJs and that, in a quarter of them, pain in TMJs negatively influenced their daily life during JIA. In addition, Leksell et al. also showed that the degrees of pain in chewing and in TMJs were significantly correlated with the scores of C-HAQ during JIA (15). Based on the pilot outcomes obtained by Leksell et al. (15), we designed the current study to evaluate the impact of TMJ arthritis on the functional disability and OHRQoL in JIA patients and to assess, by a regression analysis, which variables, such as JIA characteristics and severity, were determining and confounding factors of TMJ arthritis. The CPQ11-14 questionnaire was chosen, in this study in order to measure, in the analysed sample, the OHRQoL, given the absence of a questionnaire to specifically assess the OHRQoL in JIA patients with TMJ arthritis. The CPQ11-14 was developed, by a group of Canadian researchers (18), with the main purpose to specifically assess the OHRQoL in children and adolescents. The use of CPQ11-14, which comprises four specific health domains such as oral symptoms, functional limitations, social well-being and emotional well-being, demonstrated encouraging results in the evaluation of the OHRQoL in children with chewing disturbances and TMJ disorders (18,36,37). CPQ questionnaires have been extensively used, during the last few years in a wide range of countries and population of children, to assess a variety of oral and orofacial disturbances. Among CPQ questionnaires, CPQ11-14 was found to be a useful instrument that evaluates the impact of oral conditions on physical and psychosocial functioning in children and pre-adolescents (18,36). More specifically, higher CPQ11–14 scores were associated with a global lower OHRQoL, in a cohort of children with TMJ disorders, symptoms of anxiety and depression (37). The association between TMJ arthritis, functional disability and reduced OHRQoL, found in our study, may be explained by the role played by the TMJs in many daily life activities such as chewing, talking and in oral health well-being maintenance (38,39). In our sample, in accordance with previous reports (2,15), JIA patients with TMJ arthritis reported eating difficulties and masticatory performance impairment (2,15,40–43). Eating difficulties, associated with poor oral hygiene and TMJ arthritis and, in general, with a lower functional disabilities during JIA were associated, in several studies, with a lower level of OHRQoL during JIA (3,44,45). The present study, however, presents some limitations. One of the main limitations is represented by the questionnaires chosen for the assessment of the functional limitation and OHRQoL, the C-HAQ and CPQ11-14, respectively. During the last few decades, several investigators have developed a variety of different questionnaires designed for assessing functional limitation during JIA (19,20,46–48). The C-HAQ, used in the present study, was previously shown to generally assess the impact of JIA during TMJ arthritis (2,22,49). However, the C-HAQ was not specifically developed to assess the impact of orofacial dysfunction on parameters correlated to oral well-being. Moreover, even the CPQ, with an oral symptom domain, is not specifically developed for the evaluation of OHRQoL in JIA patients. Moreover, most of the studies on the quality of life during JIA were performed before the biological drugs were available. The questionnaires aimed at measuring the OHRQoL in JIA patients with TMJ arthritis should be now re-evaluated and re-organized in the light of the therapies of JIA patients with biological drugs, in which functional limitations are less common. For these reasons, more elaborate and specific questionnaires, specifically designed for JIA patients, should be developed for the future to assess the OHRQoL during JIA. Hopefully, future research on this topic will address more specifically the psychometric properties and internal validity of OHRQoL measures using structural equation modelling and specific item response theory in JIA patients with TMJ arthritis. Another limitation of the present study is that some variables chosen as confounding factors may have interfered with the final analysis of the determining factors of TMJ arthritis. In conclusion, in the light of the limitations of the present study, the results of this study seem to suggest an association between TMJ arthritis, functional disability (emotional and social well-being) and OHRQoL in JIA patients. TMJ arthritis was associated with high JIA duration and activity and influenced some daily activities, such as eating, hygiene, emotional and social well-being, especially in female subjects. However, these pivotal results are promising but demand further studies on a larger sample and with more elaborate and specific OHRQoL questionnaires to understand better the role and impact of TMJ arthritis on the quality of life in patients affected by JIA. Author Contributions and Acknowledgements All authors were involved in drafting the article. GI and GM conceived the study, have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of data analysis. GI, LP and GM participated in its design and the coordination of the draft and final version of the manuscript. MM, MM, DD, AA and VG collected and developed the clinical and MRI data of the analysed sample. The study was registered at clinicaltrials.gov (ID: NCT03008681). Funding This work was carried out with departmental funding only. Conflict of Interest The authors declare no conflict of interest for the work described in the manuscript. References 1. Manners , P.J. and Bower , C . ( 2002 ) Worldwide prevalence of juvenile arthritis why does it vary so much ? The Journal of Rheumatology , 29 , 1520 – 1530 . 2. Weiss , P.F. , Arabshahi , B. , Johnson , A. , Bilaniuk , L.T. , Zarnow , D. , Cahill , A.M. , Feudtner , C. and Cron , R.Q . ( 2008 ) High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound . Arthritis and Rheumatism , 58 , 1189 – 1196 . Google Scholar CrossRef Search ADS 3. Arvidsson , L.Z. , Smith , H.J. , Flatø , B. and Larheim , T.A . ( 2010 ) Temporomandibular joint findings in adults with long-standing juvenile idiopathic arthritis: CT and MR imaging assessment . Radiology , 256 , 191 – 200 . Google Scholar CrossRef Search ADS 4. Küseler , A. , Pedersen , T.K. , Gelineck , J. and Herlin , T . ( 2005 ) A 2 year followup study of enhanced magnetic resonance imaging and clinical examination of the temporomandibular joint in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 32 , 162 – 169 . 5. Isola , G. , Ramaglia , L. , Cordasco , G. , Lucchese , A. , Fiorillo , L. and Matarese , G . ( 2017 ) The effect of a functional appliance in the management of temporomandibular joint disorders in patients with juvenile idiopathic arthritis . Minerva Stomatologica , 66 , 1 – 8 . 6. Müller , L. , Kellenberger , C.J. , Cannizzaro , E. , Ettlin , D. , Schraner , T. , Bolt , I.B. , Peltomäki , T. and Saurenmann , R.K . ( 2009 ) Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging . Rheumatology (Oxford, England) , 48 , 680 – 685 . Google Scholar CrossRef Search ADS 7. Huntjens , E. , Kiss , G. , Wouters , C. and Carels , C . ( 2008 ) Condylar asymmetry in children with juvenile idiopathic arthritis assessed by cone-beam computed tomography . European Journal of Orthodontics , 30 , 545 – 551 . Google Scholar CrossRef Search ADS 8. Fjeld , M. , Arvidsson , L. , Smith , H.J. , Flatø , B. , Ogaard , B. and Larheim , T . ( 2010 ) Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood . Pediatric Rheumatology Online Journal , 8 , 13 . Google Scholar CrossRef Search ADS 9. Matarese , G. , Isola , G. , Alibrandi , A. , Lo Gullo , A. , Bagnato , G. , Cordasco , G. and Perillo , L . ( 2016 ) Occlusal and MRI characterizations in systemic sclerosis patients: A prospective study from Southern Italian cohort . Joint, Bone, Spine: Revue du Rhumatisme , 83 , 57 – 62 . Google Scholar CrossRef Search ADS 10. Engström , A.L. , Wänman , A. , Johansson , A. , Keshishian , P. and Forsberg , M . ( 2007 ) Juvenile arthritis and development of symptoms of temporomandibular disorders: a 15-year prospective cohort study . Journal of Orofacial Pain , 21 , 120 – 126 . 11. Bakke , M. , Zak , M. , Jensen , B.L. , Pedersen , F.K. and Kreiborg , S . ( 2001 ) Orofacial pain, jaw function, and temporomandibular disorders in women with a history of juvenile chronic arthritis or persistent juvenile chronic arthritis . Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics , 92 , 406 – 414 . Google Scholar CrossRef Search ADS 12. Twilt , M. , Mobers , S.M. , Arends , L.R. , ten Cate , R. and van Suijlekom-Smit , L . ( 2004 ) Temporomandibular involvement in juvenile idiopathic arthritis . The Journal of Rheumatology , 31 , 1418 – 1422 . 13. Oliveira , S. et al. ; Pediatric Rheumatology International Trials Organization (PRINTO) . ( 2007 ) Proxy-reported health-related quality of life of patients with juvenile idiopathic arthritis: the Pediatric Rheumatology International Trials Organization multinational quality of life cohort study . Arthritis and Rheumatism , 57 , 35 – 43 . Google Scholar CrossRef Search ADS 14. Bruns , A. , Hilário , M.O. , Jennings , F. , Silva , C.A. and Natour , J . ( 2008 ) Quality of life and impact of the disease on primary caregivers of juvenile idiopathic arthritis patients . Joint, Bone, Spine: Revue Du Rhumatisme , 75 , 149 – 154 . Google Scholar CrossRef Search ADS 15. Leksell , E. , Ernberg , M. , Magnusson , B. and Hedenberg-Magnusson , B . ( 2012 ) Orofacial pain and dysfunction in children with juvenile idiopathic arthritis: a case-control study . Scandinavian Journal of Rheumatology , 41 , 375 – 378 . Google Scholar CrossRef Search ADS 16. Ahola , K. , Saarinen , A. , Kuuliala , A. , Leirisalo-Repo , M. , Murtomaa , H. and Meurman , J.H . ( 2015 ) Impact of rheumatic diseases on oral health and quality of life . Oral Diseases , 21 , 342 – 348 . Google Scholar CrossRef Search ADS 17. Tollisen , A. , Selvaag , A.M. , Aulie , H.A. , Lilleby , V. , Aasland , A. , Lerdal , A. and Flatø , B . ( 2018 ) Physical functioning, pain and health-related quality of life in adults with juvenile idiopathic arthritis: A longitudinal 30-year follow-up study . Arthritis Care and Research (Hoboken) , 70, 741 – 749 . 18. Jokovic , A. , Locker , D. , Stephens , M. , Kenny , D. , Tompson , B. and Guyatt , G . ( 2002 ) Validity and reliability of a questionnaire for measuring child oral-health-related quality of life . Journal of Dental Research , 81 , 459 – 463 . Google Scholar CrossRef Search ADS 19. Gherunpong , S. , Tsakos , G. and Sheiham , A . ( 2004 ) Developing and evaluating an oral health-related quality of life index for children; the CHILD-OIDP . Community Dental Health , 21 , 161 – 169 . 20. Carle , A.C. , Dewitt , E.M. and Seid , M . ( 2011 ) Measures of health status and quality of life in juvenile rheumatoid arthritis: Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module 3.0, Juvenile Arthritis Quality of Life Questionnaire (JAQQ), Paediatric Rheumatology Quality of Life Scale (PRQL), and Childhood Arthritis Health Profile (CAHP) . Arthritis Care & Research , 63 ( Suppl 11 ), S438 – S445 . Google Scholar CrossRef Search ADS 21. Ruperto , N. , Ravelli , A. , Pistorio , A. , Malattia , C. , Cavuto , S. , Gado-West , L. , Tortorelli , A. , Landgraf , J.M. , Singh , G. and Martini , A .; Paediatric Rheumatology International Trials Organisation . ( 2001 ) Cross-cultural adaptation and psychometric evaluation of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ) in 32 countries. Review of the general methodology . Clinical and Experimental Rheumatology , 19 , S1 – S9 . 22. Frid , P. et al. ; Paediatric Rheumatology International Trials Organisation . ( 2017 ) Temporomandibular joint involvement in association with quality of life, disability, and high disease activity in juvenile idiopathic arthritis . Arthritis Care & Research , 69 , 677 – 686 . Google Scholar CrossRef Search ADS 23. Barbosa , T.d.e.S. , Tureli , M.C. , Nobre-dos-Santos , M. , Puppin-Rontani , R.M. and Gavião , M.B . ( 2013 ) The relationship between oral conditions, masticatory performance and oral health-related quality of life in children . Archives of Oral Biology , 58 , 1070 – 1077 . Google Scholar CrossRef Search ADS 24. Paula , J.S. , Meneghim , M.C. , Pereira , A.C. and Mialhe , F.L . ( 2015 ) Oral health, socio-economic and home environmental factors associated with general and oral-health related quality of life and convergent validity of two instruments . BMC Oral Health , 15 , 26 . Google Scholar CrossRef Search ADS 25. Cassidy , J.T. , Petty , R.E. , Laxer , R. and Lindsley , C . ( 2011 ) Textbook of pediatric rheumatology , 6th ed . Saunders , Philadelphia , pp. 71 – 304 . 26. Sheppard , I.M. and Sheppard , S.M . ( 1965 ) Maximal incisal opening–a diagnostic index ? The Journal of Dental Medicine , 20 , 13 – 15 . 27. Koos , B. , Twilt , M. , Kyank , U. , Fischer-Brandies , H. , Gassling , V. and Tzaribachev , N . ( 2014 ) Reliability of clinical symptoms in diagnosing temporomandibular joint arthritis in juvenile idiopathic arthritis . The Journal of Rheumatology , 41 , 1871 – 1877 . Google Scholar CrossRef Search ADS 28. Cannizzaro , E. , Schroeder , S. , Müller , L.M. , Kellenberger , C.J. and Saurenmann , R.K . ( 2011 ) Temporomandibular joint involvement in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 38 , 510 – 515 . Google Scholar CrossRef Search ADS 29. Kirkhus , E. , Arvidsson , L.Z. , Smith , H.J. , Flatø , B. , Hetlevik , S.O. and Larheim , T.A . ( 2016 ) Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis . Pediatric Radiology , 46 , 331 – 341 . Google Scholar CrossRef Search ADS 30. Raucci , G. , Pachêco-Pereira , C. , Grassia , V. , d’Apuzzo , F. , Flores-Mir , C. and Perillo , L . ( 2015 ) Maxillary arch changes with transpalatal arch treatment followed by full fixed appliances . The Angle Orthodontist , 85 , 683 – 689 . Google Scholar CrossRef Search ADS 31. Hsieh , Y.J. , Darvann , T.A. , Hermann , N.V. , Larsen , P. , Liao , Y.F. , Bjoern-Joergensen , J. and Kreiborg , S . ( 2016 ) Facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint involvement . American Journal of Orthodontics and Dentofacial Orthopedics , 149 , 182 – 191 . Google Scholar CrossRef Search ADS 32. Isola , G. , Anastasi , G.P. , Matarese , G. , Williams , R.C. , Cutroneo , G. , Bracco , P. and Piancino , M.G . ( 2017 ) Functional and molecular outcomes of the human masticatory muscles . Oral Diseases , 1 – 14 . doi: 10.1111/odi.12806. [Epub ahead of print.] 33. Präger , T.M. , Meyer , P. , Rafayelyan , S. , Minden , K. and Jost-Brinkmann , P.G . ( 2015 ) Effect of methotrexate on the mandibular development of arthritic rabbits . European Journal of Orthodontics , 37 , 514 – 521 . Google Scholar CrossRef Search ADS 34. Moretti , C. , Viola , S. , Pistorio , A. , Magni-Manzoni , S. , Ruperto , N. , Martini , A. and Ravelli , A . ( 2005 ) Relative responsiveness of condition specific and generic health status measures in juvenile idiopathic arthritis . Annals of the Rheumatic Diseases , 64 , 257 – 261 . Google Scholar CrossRef Search ADS 35. Pedersen , T.K. , Küseler , A. , Gelineck , J. and Herlin , T . ( 2008 ) A prospective study of magnetic resonance and radiographic imaging in relation to symptoms and clinical findings of the temporomandibular joint in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 35 , 1668 – 1675 . 36. Jokovic , A. , Locker , D. , Tompson , B. and Guyatt , G . ( 2004 ) Questionnaire for measuring oral health-related quality of life in eight- to ten-year-old children . Pediatric Dentistry , 26 , 512 – 518 . 37. Barbosa , T.S. , Gavião , M.B. , Leme , M.S. and Castelo , P.M . ( 2016 ) Oral Health-related Quality of Life in Children and Preadolescents with Caries, Malocclusions or Temporomandibular Disorders . Oral Health & Preventive Dentistry , 14 , 389 . 38. Ostile , I.L. , Johansson , I. , Aasland , A. , Flatö , B. and Möller , A . ( 2010 ) Self-rated physical and psychosocial health in a cohort of young adults with juvenile idiopathic arthritis . Scandinavian Journal of Rheumatology , 39 , 318 – 325 . Google Scholar CrossRef Search ADS 39. Isola , G. , Matarese , G. , Cordasco , G. , Perillo , L. and Ramaglia , L . ( 2016 ) Mechanobiology of the tooth movement during the orthodontic treatment: a literature review . Minerva Stomatologica , 65 , 299 – 327 . 40. Peltomäki , T. , Kreiborg , S. , Pedersen , T.K. , Ogaard , B. and Welbury , R.R . ( 2015 ) Craniofacial growth and dento-alveolar development in juvenile idiopathic arthritis patients . Seminars in Orthodontics , 21 , 84 – 93 . Google Scholar CrossRef Search ADS 41. Cavuoti , S. , Matarese , G. , Isola , G. , Abdolreza , J. , Femiano , F. and Perillo , L . ( 2016 ) Combined orthodontic-surgical management of a transmigrated mandibular canine . The Angle Orthodontist , 86 , 681 – 691 . Google Scholar CrossRef Search ADS 42. Stoustrup , P. , Küseler , A. , Kristensen , K.D. , Herlin , T. and Pedersen , T.K . ( 2013 ) Orthopaedic splint treatment can reduce mandibular asymmetry caused by unilateral temporomandibular involvement in juvenile idiopathic arthritis . European Journal of Orthodontics , 35 , 191 – 198 . Google Scholar CrossRef Search ADS 43. Piancino , M.G. , Cannavale , R. , Dalmasso , P. , Tonni , I. , Filipello , F. , Perillo , L. , Cattalini , M. and Meini , A . ( 2015 ) Condylar asymmetry in patients with juvenile idiopathic arthritis: Could it be a sign of a possible temporomandibular joints involvement ? Seminars in Arthritis and Rheumatism , 45 , 208 – 213 . Google Scholar CrossRef Search ADS 44. Isola , G. , Matarese , G. , Cordasco , G. , Rotondo , F. , Crupi , A. and Ramaglia , L . ( 2015 ) Anticoagulant therapy in patients undergoing dental interventions: a critical review of the literature and current perspectives . Minerva Stomatologica , 64 , 21 – 46 . 45. Stoustrup , P. et al. ; euroTMjoint Research Network . ( 2017 ) Clinical Orofacial Examination in Juvenile Idiopathic Arthritis: International Consensus-based Recommendations for Monitoring Patients in Clinical Practice and Research Studies . The Journal of Rheumatology , 44 , 326 – 333 . Google Scholar CrossRef Search ADS 46. Kristensen , K.D. , Stoustrup , P. , Küseler , A. , Pedersen , T.K. , Twilt , M. and Herlin , T . ( 2016 ) Clinical predictors of temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic literature review . Seminars in Arthritis and Rheumatism , 45 , 717 – 732 . Google Scholar CrossRef Search ADS 47. Ferlazzo , N. , Currò , M. , Zinellu , A. , Caccamo , D. , Isola , G. , Ventura , V. , Carru , C. , Matarese , G. and Ientile , R . ( 2017 ) Influence of MTHFR genetic background on p16 and MGMT methylation in oral squamous cell cancer . International Journal of Molecular Sciences , 29 , 18 . pii: E724. 48. Twilt , M. , Schulten , A.J. , Verschure , F. , Wisse , L. , Prahl-Andersen , B. and van Suijlekom-Smit , L.W . ( 2008 ) Long-term followup of temporomandibular joint involvement in juvenile idiopathic arthritis . Arthritis and Rheumatism , 59 , 546 – 552 . Google Scholar CrossRef Search ADS 49. Stoustrup , P.B. , Ahlefeldt-Laurvig-Lehn , N. , Kristensen , K.D. , Arvidsson , L.Z. , Twilt , M. , Cattaneo , P.M. , Küseler , A. , Christensen , A.E. , Herlin , T. and Pedersen , T.K . ( 2018 ) No association between types of unilateral mandibular condylar abnormalities and facial asymmetry in orthopedic-treated patients with juvenile idiopathic arthritis . American Journal of Orthodontics and Dentofacial Orthopedics , 153 , 214 – 223 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices) http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The European Journal of Orthodontics Oxford University Press

The impact of temporomandibular joint arthritis on functional disability and global health in patients with juvenile idiopathic arthritis

Loading next page...
 
/lp/ou_press/the-impact-of-temporomandibular-joint-arthritis-on-functional-8tOYD3k2B5
Publisher
Oxford University Press
Copyright
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com
ISSN
0141-5387
eISSN
1460-2210
D.O.I.
10.1093/ejo/cjy034
Publisher site
See Article on Publisher Site

Abstract

Summary Objectives The objective of the study was to evaluate the impact of temporomandibular joint (TMJ) arthritis on the functional disability and quality of life in patients affected by juvenile idiopathic arthritis (JIA). Materials and Methods Sixty-two consecutive patients with JIA with or without TMJ arthritis and 35 healthy control subjects were enrolled in the study. The demographic data, disease activity and clinical characteristics were obtained from all patients. The functional disability was assessed using the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ). The oral health-related quality of life (OHRQoL) was assessed using the Child Perception Questionnaire (CPQ11-14). Possible determining factors of TMJ arthritis comprised demographic, disease characteristics and scores derived from questionnaires that were assessed by a uni and multivariable logistic regression analysis. Results Compared with patients without TMJs arthritis, JIA patients with TMJ arthritis presented higher functional disability. The multivariable logistic regression analysis performed showed that female subjects (OR = 1.5, P = 0.041), with a JIA duration over 3.9 years (OR = 2.7, P = 0.033) and presenting higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis. Conclusions JIA patients with TMJ arthritis presented higher functional disability and lower OHRQoL scores compared with JIA patients without TMJ arthritis. TMJ arthritis was strongly associated with JIA duration and activity, especially in female patients. Introduction Juvenile idiopathic arthritis (JIA) is a chronic disease of unknown ethiology, with an estimated incidence of 16 to 150 cases per 100000 children worldwide, characterized by chronic synovitis in one or many joints and represents an important cause of disability in childhood (1). Temporomandibular joint (TMJ) arthritis is a common consequence of the systemic disease in patients with JIA (2,3). Previous reports have shown that up to 93% of patients with JIA may present early inflammatory findings in TMJs (4,5). During JIA, the impairment due to TMJ arthritis may lead to difficulties in many daily activities, such as eating, smiling and performing oral hygiene (6). The appearance of TMJ arthritis in JIA patients was shown to perhaps also determine, if not properly treated, a reduced and asymmetric craniofacial growth with the appearance of skeletal malocclusions and micrognathia (7–9). In JIA patients, the appearance of TMJ arthritis during childhood has been demonstrated to determine a high percentage of TMJ and orofacial disorders up to 26 years from JIA disease onset (10,11). The diagnosis of TMJ arthritis in JIA patients during the active phases of the disease is a challenging task. In fact, previous reports showed that pain, one of the main factors associated with TMJ arthritis, is a very unreliable sign of disease because it is reported in only a quarter of JIA patients with the presence of manifest radiological signs of TMJ arthritis (2,12). However, the presence of TMJ involvement during JIA has been demonstrated to influence the quality of life of JIA patients (13) and to be a significant burden on patient’s caregivers (14). Due to the involvement of TMJs, orofacial pain is a frequent finding during JIA and is reported to severely affect daily life in almost 25% of cases (15). For many years, several health-related quality of life (HRQoL) questionnaires have been developed to detect the global impact of JIA on the daily quality of life and the patient-relevant burden of patients affected by JIA (16,17). During the last few decades, the Child Oral Health Quality of Life Instrument (COHQOL) (18), the Child Oral Impact on Daily Performances (Child-OIDP) (19), the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module 3.0, the Juvenile Arthritis Quality of Life Questionnaire (JAQQ), the Paediatric Rheumatology Quality of Life Scale (PRQL), and the Childhood Arthritis Health Profile (CAHP) (20) have been used to measure the health status and the subjective burden of disease during JIA. However, an advanced generation of questionnaires has been developed to more appropriately assess the global functional disability and daily functions in children, such as the Childhood Health Assessment Questionnaire (C-HAQ) and the Child Perception Questionnaire (CPQ11-14), both of them translated into many different languages (21). C-HAQ and CPQ11-14, with its disease-specific sections, have been validated to estimate functional assessment during JIA (22). C-HAQ has been shown to specifically determine a child’s ability to perform different daily functions at disease onset during JIA, such as dressing, grooming, arising, eating, walking, hygiene, reach and grip (2,22). However, in order to better understand the impact that certain oral conditions cause on the overall quality of life, CPQ11–14 has been developed with the main purpose of assessing the oral HRQoL (OHRQoL) in children and adolescents by four domains: oral symptoms, functional limitations, emotional and social well-being (23,24). As a negative impact of arthritis in TMJs during JIA, there is an increasing interest concerning the impact that TMJ arthritis exerts on the HRQoL in JIA patients. In light of these findings, the aim of this study was to assess the impact induced by TMJ arthritis on functional disability and OHRQoL in a cohort of patients affected by JIA with or without TMJ arthritis compared with healthy subjects and to determine what the greatest determining factors of TMJ arthritis were. The null hypothesis to invalidate was that JIA patients with and without TMJ arthritis presented no differences in clinical characteristics, functional disability and OHRQoL. Materials and methods Study design Patients with a diagnosis of JIA performed in accordance with ILAR criteria (25), with and without TMJ arthritis were enrolled in the present case–control study between February 2012 and September 2017. The ethical committee of the University of Messina approved the protocol of the study (#918-10, 5 February 2010). The study was registered at clinicaltrials.gov (ID: NCT03008681). The written informed consent was acquired from the parents of each patient who were informed about the study type and characteristics, in accordance with the Declaration of Helsinki in 1975, revised in 2000. The inclusion criteria were: 1. diagnosis of JIA (only in JIA groups) and 2. no injections of any steroid on TMJ during the last 12 months. The exclusion criteria were: 1. previous orthodontic treatment, 2 previous maxillofacial surgery and 3. genetic or congenital syndromes or any concurrent medical condition that could influence the results of the study. Seventy-two consecutive patients with a diagnosis of JIA aged between 8 and 17 years (38 female and 34 males, mean age of 11.2 ± 2.2 years) were initially enrolled as the study group. Thirty-five healthy subjects chosen from all patients attending dental clinics for routine oral visits, who were matched for age and sex (17 female and 18 males, mean age of 11.9 ± 2.2 years), were enrolled as the control group. The healthy subjects did not have any history of rheumatic, congenital or systemic diseases or TMJ disorders and presented a good occlusion and maxillary relationship. After the first screening, 10 patients with JIA were excluded because they did not fully meet the inclusion criteria (n = 4), declined to participate (n = 2) or missed the clinical examination (n = 4). Thus, the final number of patients assessed for eligibility as the JIA group was 62. Data collection The clinical characteristics data and subtype of JIA was obtained from the hospital chart of each patient and was documented by a paediatric rheumatologist (Table 1). Table 1. Sociodemographic and clinical characteristics of the study population. Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Values are expressed with mean (±SD). View Large Table 1. Sociodemographic and clinical characteristics of the study population. Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Characteristics Group 1 (n = 32) Group 2 (n = 30) Group 3 (n = 35) Age, mean ± SD 11.9 ± 2.3 12.1 ± 2.5 11.8 ± 2.2 Female sex, no. (%) 17 (53.1) 14 (46.6) 15 (57.7) Patients <9 years old, no. (%) 1 (3.1) 1 (3.3) — BMI, mean ± SD kg/m2 20.6 ± 6.5 21.1 ± 5.8 20.4 ± 5.2 JIA subtype, no. (%) Systemic JIA 11 (34.4) 10 (33.3) — RF-negative polyarthritis 9 (28.1) 7 (23.3) — RF-positive polyarthritis 4 (12.5) 5 (16.6) — Enthesitis-related arthritis 1 (3.1) — — Psoriasic arthritis 2 (6.2) 1 (3.3) — Extended oligoarthritis 5 (15.6) 6 (20) — Undifferentiated arthritis — 1 (3.3) — Age at disease onset, mean ± years 8.9 ± 3.4 8.4 ± 2.8 — No. of JIA patients with active joint, (%) 19 (59.4) 17 (56.6) — No. of active Joint in JIA patients (median) 8.0 ± 3.6 3.0 ± 3.1 — No. of joints with pain (median) 6.0 ± 2.1 3.0 ± 1.9 — Current morning stiffness >15 min, no. (%) 9 (28.1) 7 (23.3) — CRP level, mean ± SD mg/dl 11.6 ± 11.2 12.7 ± 13.4 5.7 ± 9.4 ESR, median 31.0 ± 6.4 21.0 ± 7.2 10.0 ± 6.5 Positive ANA test at baseline, no. (%) 10 (31.2) 12 (40) — Positive HLA-B27 test, no. (%) 7 (21.9) 9 (30) — Any comorbidity, no. (%) 14 (43.7) 11 (36.6) — History of uveitis, no. (%) 7 (21.8) 6 (20) — Biological drugs Etanercept, no. (%) 15 (46.9) 10 (33.3) — Adalinumab, no. (%) 3 (9.3) 5 (16.6) — DMARD treatment Methotrexate, no. (%) 13 (40.6) 11 (36.6) — chloroquine/hydroxychloroquine, no. (%) 3 (9.3) 2 (6.6) — azathioprine, no. (%) 2 (6.2) 1 (3.3) — Cyclosporin A, no. (%) — 1 (3.3) — TMJ characteristics Maximum mouth opening, mm ± SD 34.2 ± 5.2 40.7 ± 4.9 43.9 ± 4.5 Laterotrusion, mm ± SD 9.1 ± 3.9 14.6 ± 3.7 17.1 ± 4.1 Protrusion, mm ± SD 4.9 ± 2.3 6.9 ± 2.7 7.7 ± 3.1 Values are expressed with mean (±SD). View Large The clinical and orthodontic assessment was performed in all patients by the same examiner who was not involved in the subsequent data analysis. The assessment comprised a full mouth evaluation and the valuation of TMJ by recording, in each patient, clicking, crepitus, anterior translation, pain with palpation and opening, symmetry during opening, capability of protrusion and laterotrusion and the maximum mouth opening. The mouth opening was measured by the Therabite Measuring Scale (Atos Medical, Milwaukee, WI), determining the differences from normal values of children up to 18 years (26). In all enrolled subjects, TMJs were evaluated by Magnetic Resonance Imaging (MRI) scans. All patients underwent Gadolinium-enhanced MRI. The MRI evaluation included coronal T1- and T2-weighted images, sagittal T1-weighted and dual-echo T2-weighted images, and, following the intravenous administration of Gadolinium contrast material, sagittal and coronal fat-saturated T1-weighted images. Axial and coronal T2 were acquired perpendicular to the mandibular condyle and parallel to the ramus of the mandible. Sagittal oblique images were acquired with 2-mm slices and a 12-cm field of view and 256 × 224 matrix. Any clinical or radiological signs at MRI of TMJ arthritis with active findings of synovitis, effusion or pannus and MRI signs of joint structural damage such as flattening of the mandibular head, flattening of the fossa and the presence of bone marrow edema, erosions or osteophytes were recorded during the first clinical and MRI examination. The study involved three groups (Table 1): group of JIA patients with TMJ arthritis (JIA+TMJ arthritis group), group of JIA patients without TMJ arthritis (JIA group) and healthy subjects group (control group). During the calibration sessions and after a clinical evaluation, intra-examiner repeatability and reproducibility was evaluated to obtain duplicate measurements of clinical parameters from patients randomly selected from the sample. One examiner evaluated the parameters of the two JIA groups and a second examiner evaluated the control group. The intra-examiner agreement, which was 0.815 (95% CI = 0.73–0.9), was obtained by calculating Cohen’s k coefficient from all outcomes deriving from the two HRQoL questionnaires and predicted a good degree of reliability. Sample size The sample size was established considering the mean prevalence of JIA in the population equal to 0.08% (1), the study group incidence of 2.8% (as the prevalence of JIA in our database), an alpha level of 0.05 and a power of 80%. A minimum sample of 51 JIA patients was determined to ensure a good sample size. Sixty-two patients affected by JIA and 26 healthy subjects in the control group were finally enrolled. Functional disability and OHRQoL measurement In the enrolled patients, functional disability was assessed by the Italian version of the C-HAQ questionnaire (21). The C-HAQ consisted of several domains aimed at evaluating the impact of the frequency of functional disability and quality of care related to daily life activities and the ability of the patient to achieve distinct functions. The C-HAQ version chosen for this study was composed of seven different domains regarding daily activities like walking, eating, arising, dressing, hygiene, gripping and reaching/activity calculated by a range from 0 (no or minimal physical disability) to 3 (very severe physical disability). To measure the parent’s global assessment of the general health of a child’s in the last 10 days a Visual Analog Scale (PRgloVAS) [0–10-cm, ranged from 0 (very health) to 10 (the poorest)] was chosen. Given the absence of a questionnaire to specifically assess the OHRQoL in JIA patients with TMJ arthritis, in the present study, we decided to adopt the Child Perception Questionnaire (CPQ11-14), which was already validated for children with TMJ disorders (18). The version of CPQ11-14, chosen for this study, comprised four health domains (oral symptoms, functional limitations, social well-being and emotional well-being) aimed at specifically measuring the impact of oral disease and the extent to which the patient’s condition affected his/her overall global well-being in the previous 3 months. In the CPQ11-14, the answer options were ‘never = 0’; ‘once or twice = 1’; ‘sometimes = 2’; ‘often = 3’; ‘every day or almost every day = 4’. The summary score following the sum of these domains ranged from 0 to 140. A low total summary score of CPQ11-14 predicted a good OHRQoL, whereas a high summary score predicted a low OHRQoL. Both questionnaires were filled out by the patient aged >9 years old or by one of the caregivers. Statistical analysis All statistical analyses were executed using a software program (SPSS version 17.0 for Windows, Chicago, IL). The parametric approach was used because the data are normally distributed, as verified by the Kolmogorov–Smirnov test. The chi-square test and the t-test were used to compare the categorical and the continuous variables, respectively. A univariable logistic regression analysis was used to assess the influence of the quality of life measurements on TMJ involvement. The same analysis was performed in order to recognize factors distinguishing JIA patients with the presence/absence of TMJ arthritis by using the C-HAQ and CPQ11-14 domains as exploratory measures. To recognize factors independently associated with TMJ arthritis, multivariable logistic regression was performed. P < 0.05 was considered to be statistically significant. Results The demographic data, age and gender distribution, JIA types, drug therapy and the serological values of the sample are presented in Table 1. A total of 88 patients participated in the study; 32 patients in the JIA+TMJ group, 30 patients in the JIA group and 26 patients in the control group. The examined groups were matched for age and gender. One patient in the JIA+TMJ arthritis group and one patient in the JIA group were <9 years old. Regarding the JIA patients, JIA was diagnosed at 8.7 ± 3.1 (SD) years of age. Of the JIA patients, 35.7% presented JIA of up to 2 years of duration, 27.8% between 2 and 5 years of duration and 36.5% more than 5 years of duration. Nine patients in the JIA+TMJ group (28.1%) and seven (23.3%) in the JIA group presented rheumatoid-factor–negative polyarthritis (Table 1). Eighteen patients (56.2%) in the JIA+TMJ group and 15 patients (50%) in the JIA group underwent DMARD at least once while 18 patients (56.2%) in the JIA+TMJ group and 15 patients (30%) in the JIA group underwent biological drugs (Table 1). In the JIA+TMJ group, 19 patients (59.4%) presented bilateral and 13 (10.6%) patients unilateral TMJ arthritis, with the presence of a hypoplastic mandibular condyle that was found bilaterally in 18 (56.2%) and unilaterally in 14 (43.8%) patients. Pain in TMJs was present, only in 19 patients in the JIA+TMJ group (59.4%). Moreover, in the JIA+TMJ group, 23 (71.9%) patients presented myofascial pain, associated in 19 patients (59.4%) with a limitation of mouth opening. Even in the JIA+TMJ group, the mean maximum mouth opening was 34.2 ± 2.3 mm, whereas in the JIA and control groups the mean values were 40.7 ± 2.3 mm and 43.9 ± 1.8 mm, respectively (Table 1). In the JIA+TMJ group, at MRI, clear signs of TMJ involvement were present in 26 patients (81.2%), of which 21 were bilateral (65.6%) and 5 unilateral (15.6%) patients. Moreover, all patients in the JIA+TMJ group showed clear signs of active TMJ arthritis, which were mild in 19 patients (59.4%) and severe in 13 patients (40.7%). Moreover, 16 patients (50%) presented condylar deformities that were mild in 9 patients (28.1%) and severe in 8 patients (25%). Regarding the C-HAQ and the CPQ11-14, patients in the JIA+TMJ group showed statistically significant differences in the disability score compared with patients in the JIA and control groups (Figure 1 and 2). Figure 1. View largeDownload slide National version of the childhood health assessment questionnaire (C-HAQ) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 1. View largeDownload slide National version of the childhood health assessment questionnaire (C-HAQ) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 2. View largeDownload slide Child Perception Questionnaire (CPQ11-14) scores of the patient sample. Results are presented as mean and confidence intervals (CI). Figure 2. View largeDownload slide Child Perception Questionnaire (CPQ11-14) scores of the patient sample. Results are presented as mean and confidence intervals (CI). As reported in Figure 1, patients in the JIA+TMJ group presented a mean score of more than twice the C-HAQ with respect to the domains related to eating, hygiene and reaching activities, and the PRgloVAS score, both significantly higher compared with patients of the other groups. Moreover, compared with the control group, patients in the JIA group presented higher, but not significant, values of dressing, eating and reaching activities. Regarding the CPQ11-14, the patients in the JIA+TMJ group presented lower scores regarding the domains of functional limitations and well-being, whereas they presented higher scores in domains of oral symptoms compared with the other two groups. Moreover, as reported in Table 2, the univariate analyses (odds ratios [ORs] with 95% confidence intervals), which assessed the association of JIA activity/disability and quality of life with TMJ arthritis, showed that, in the JIA+TMJ group, a significant association was found between TMJ arthritis and the C-HAQ and CPQ11-14 domains. Disease activity and disability were higher in the patients in the JIA+TMJ group which presented higher values especially for eating (OR = 5.8, P = 0.015), hygiene (OR = 3.4, P = 0.028) and in the PRgloVAS score (OR = 3.6, P = 0.037). Regarding the CPQ11-14 domains, the JIA+TMJ group presented higher scores compared with the other two groups regarding oral symptoms and functional limitations (OR = 2.4, P = 0.013 and OR = 3.7, P = 0.021, respectively). Table 2. Univariable logistic regression analysis of the quality of life measurements of the patient sample. Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Values expressed OR (95% CI); ns, not significant. View Large Table 2. Univariable logistic regression analysis of the quality of life measurements of the patient sample. Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Parameters TMJs involvement OR (95% CI) P value C-HAQ  Eating 5.8 (2.4–6.9) 0.015  Dressing 3.1 (2.3–4.5) ns  Walking 2.5 (1.5–3.9) ns  Arising 3.2 (2.4–5.6) ns  Grip 3.3 (2.6–4.9) ns  Hygiene 3.4 (2.1–4.6) 0.028  Reach 3.3 (1.8–5.5) ns  PRgloVAS 3.6 (2.3–5.5) 0.037 CPQ11-14  Oral symptoms 2.4 (1.6–4.5) 0.013  Functional limitations 3.7 (2.1–4.8) 0.021  Emotional well-being 2.2 (1.4–3.1) ns  Social well-being 2.3 (1.3–2.9) ns Values expressed OR (95% CI); ns, not significant. View Large In the final regression model, all variables significantly related to TMJ arthritis were selected, in the univariate analysis, based on OR such as gender, JIA duration, RF, number of active joints, ESR, C-HAQ and CPQ11-14 global scores. In order to validate also for the level of disease activity, in the final model, the score results were adjusted with the OR for the RF values and the number of active joints. The multivariable analysis demonstrated that variables such as the female gender (OR = 1.5, P = 0.041), JIA duration over 3.9 years (OR = 2.7, P = 0.033) and having higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis (Table 3). Table 3. Multivariable logistic regression analysis of quality of life measures, disease activity and clinical and demographic characteristics associated with TMJ involvement. Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns ns, not significant. View Large Table 3. Multivariable logistic regression analysis of quality of life measures, disease activity and clinical and demographic characteristics associated with TMJ involvement. Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns Parameters Crude OR (95% CI) Adjusted OR (95% CI) Significance C-HAQ total score > 1.3 3.8 (1.5–5.8) 2.7 (2.4–5.6) 0.012 CPQ11-14 total score > 1.4 3.2 (1.3–4.8) 2.9 (2.4–6.9) 0.015 Disease duration >3.9 years 2.3 (1.9–2.9) 2.7 (2.3–4.5) 0.033 Female sex 1.4 (1.1–1.9) 1.5 (1.3–3.9) 0.041 PRgloVAS > 2.1 3.6 (2.3–5.5) 1.7 (1.3–3.7) ns ns, not significant. View Large For the multivariate model, all the measures on the correct fit were calculated; adjusted R2 = 0.702, residuals degrees of freedom = 83; a significance level of the model P = 0.001, so we obtained satisfactory results that guarantee an adequate degree of fit to the data. Moreover, the non-significance of the Deviance test and the Pearson test (P = 0.950 and 0.991, respectively) leads to accepting the hypothesis that there are no significant differences between the observed values and the theoretical ones, deriving from the adopted model. Discussion The objective of this study was to evaluate the impact of TMJ arthritis and its determining factors on functional disability and OHRQoL in patients affected by JIA. The present study showed an association between JIA disease duration and activity and TMJ arthritis in patients affected by JIA. In our cohort, patients with JIA and TMJ arthritis presented more functional disability (assessed by C-HAQ) and lower OHRQoL (assessed by CPQ11-14) compared with JIA patients without TMJ arthritis and healthy subjects. Moreover, there was an independent strict association between TMJ arthritis and the duration of JIA <3.9 years, especially in female patients. In our sample, a high proportion of JIA patients presented TMJ involvement (52%). The diagnosis of TMJ arthritis was performed, in accordance with previous studies, by a combined clinical and MRI evaluation of TMJs that detected, more specifically, the presence of TMJ arthritis (4,27). The associations found in our study, between TMJ arthritis and JIA disease characteristics (70% in total), were in accordance with previous clinical and radiological studies (5,28) that reported signs of TMJ arthritis, in JIA patients, in a proportion from 40% to 85% (29). TMJ arthritis comprises a group of different signs and symptoms of dysfunctions in TMJs, including facial and muscular pain and click (30,31). However, even if it was reported as a frequent finding in JIA patients, TMJ arthritis, although present, in most of JIA patients is an asymptomatic disease, especially at a young age (2,12,32). Indeed, in our sample, a frequency of clinical pain in TMJs was observed in only 59.4% of JIA patients who, however, presented a high percentage of clear signs of TMJ arthritis at MRI (81.2%). In accordance with our results, previous studies demonstrated that clear signs of pain in TMJs, one of the better predictors of arthritis and joint destruction in TMJs, are usually reported in only 14–20% of patients in which clear radiological signs of TMJ arthritis are present (2,12). Moreover, this study showed that JIA patients with TMJ arthritis presented a significant higher functional disability and daily difficulties (high mean score of C-HAQ) compared with JIA patients without TMJ arthritis and to healthy subjects. In accordance with our results, previous reports demonstrated that TMJ arthritis and dysfunctions negatively influenced the daily functions and quality of life in JIA patients (17,22,33). JIA patients usually present severe articular symptoms, such as pain, joint contracture or large effusion, and a rapid clinical improvement that often ensues may have a relevant impact on their psychosocial health, leading to a detectable improvement in their emotional well-being, behavior or self-esteem (33,34). Moretti et al. (34) indicated that the C-HAQ questionnaire is a comprehensive tool that evaluates the physician’s global assessment of the disease and the relative responsiveness of condition-specific measures after intra-articular corticosteroid injection during JIA. Moreover, Ruperto et al. showed that the Italian versions of the C-HAQ/CHQ presented a reliable and valid tool to capture the functional, physical and psychosocial well-being of children with JIA (21). More specifically, Weiss et al. (2), in a cohort of children with a new-onset of JIA, found that JIA patients with TMJ dysfunction and orofacial symptoms presented low C-HAQ scores. In the study of Weiss et al. (2), the C-HAQ score was tested for the assessment of JIA disease activity and disability in JIA patients with MRI and ultrasound findings of TMJ arthritis. Moreover, Frid et al. (22), on a cross-sectional cohort of 3343 children with JIA also found that C-HAQ and PRgloVAS scores were useful tools to assess the functional disability in JIA patients with TMJ. In accordance with the results of our study, previous reports demonstrated that JIA patients showed a strong relationship between TMJ arthritis and high functional disability and low quality of life (2,6,11,12,15,35). Leksell et al. (15) demonstrated, in a clinical study, that almost 80% of JIA patients presented pain in TMJs and that, in a quarter of them, pain in TMJs negatively influenced their daily life during JIA. In addition, Leksell et al. also showed that the degrees of pain in chewing and in TMJs were significantly correlated with the scores of C-HAQ during JIA (15). Based on the pilot outcomes obtained by Leksell et al. (15), we designed the current study to evaluate the impact of TMJ arthritis on the functional disability and OHRQoL in JIA patients and to assess, by a regression analysis, which variables, such as JIA characteristics and severity, were determining and confounding factors of TMJ arthritis. The CPQ11-14 questionnaire was chosen, in this study in order to measure, in the analysed sample, the OHRQoL, given the absence of a questionnaire to specifically assess the OHRQoL in JIA patients with TMJ arthritis. The CPQ11-14 was developed, by a group of Canadian researchers (18), with the main purpose to specifically assess the OHRQoL in children and adolescents. The use of CPQ11-14, which comprises four specific health domains such as oral symptoms, functional limitations, social well-being and emotional well-being, demonstrated encouraging results in the evaluation of the OHRQoL in children with chewing disturbances and TMJ disorders (18,36,37). CPQ questionnaires have been extensively used, during the last few years in a wide range of countries and population of children, to assess a variety of oral and orofacial disturbances. Among CPQ questionnaires, CPQ11-14 was found to be a useful instrument that evaluates the impact of oral conditions on physical and psychosocial functioning in children and pre-adolescents (18,36). More specifically, higher CPQ11–14 scores were associated with a global lower OHRQoL, in a cohort of children with TMJ disorders, symptoms of anxiety and depression (37). The association between TMJ arthritis, functional disability and reduced OHRQoL, found in our study, may be explained by the role played by the TMJs in many daily life activities such as chewing, talking and in oral health well-being maintenance (38,39). In our sample, in accordance with previous reports (2,15), JIA patients with TMJ arthritis reported eating difficulties and masticatory performance impairment (2,15,40–43). Eating difficulties, associated with poor oral hygiene and TMJ arthritis and, in general, with a lower functional disabilities during JIA were associated, in several studies, with a lower level of OHRQoL during JIA (3,44,45). The present study, however, presents some limitations. One of the main limitations is represented by the questionnaires chosen for the assessment of the functional limitation and OHRQoL, the C-HAQ and CPQ11-14, respectively. During the last few decades, several investigators have developed a variety of different questionnaires designed for assessing functional limitation during JIA (19,20,46–48). The C-HAQ, used in the present study, was previously shown to generally assess the impact of JIA during TMJ arthritis (2,22,49). However, the C-HAQ was not specifically developed to assess the impact of orofacial dysfunction on parameters correlated to oral well-being. Moreover, even the CPQ, with an oral symptom domain, is not specifically developed for the evaluation of OHRQoL in JIA patients. Moreover, most of the studies on the quality of life during JIA were performed before the biological drugs were available. The questionnaires aimed at measuring the OHRQoL in JIA patients with TMJ arthritis should be now re-evaluated and re-organized in the light of the therapies of JIA patients with biological drugs, in which functional limitations are less common. For these reasons, more elaborate and specific questionnaires, specifically designed for JIA patients, should be developed for the future to assess the OHRQoL during JIA. Hopefully, future research on this topic will address more specifically the psychometric properties and internal validity of OHRQoL measures using structural equation modelling and specific item response theory in JIA patients with TMJ arthritis. Another limitation of the present study is that some variables chosen as confounding factors may have interfered with the final analysis of the determining factors of TMJ arthritis. In conclusion, in the light of the limitations of the present study, the results of this study seem to suggest an association between TMJ arthritis, functional disability (emotional and social well-being) and OHRQoL in JIA patients. TMJ arthritis was associated with high JIA duration and activity and influenced some daily activities, such as eating, hygiene, emotional and social well-being, especially in female subjects. However, these pivotal results are promising but demand further studies on a larger sample and with more elaborate and specific OHRQoL questionnaires to understand better the role and impact of TMJ arthritis on the quality of life in patients affected by JIA. Author Contributions and Acknowledgements All authors were involved in drafting the article. GI and GM conceived the study, have full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of data analysis. GI, LP and GM participated in its design and the coordination of the draft and final version of the manuscript. MM, MM, DD, AA and VG collected and developed the clinical and MRI data of the analysed sample. The study was registered at clinicaltrials.gov (ID: NCT03008681). Funding This work was carried out with departmental funding only. Conflict of Interest The authors declare no conflict of interest for the work described in the manuscript. References 1. Manners , P.J. and Bower , C . ( 2002 ) Worldwide prevalence of juvenile arthritis why does it vary so much ? The Journal of Rheumatology , 29 , 1520 – 1530 . 2. Weiss , P.F. , Arabshahi , B. , Johnson , A. , Bilaniuk , L.T. , Zarnow , D. , Cahill , A.M. , Feudtner , C. and Cron , R.Q . ( 2008 ) High prevalence of temporomandibular joint arthritis at disease onset in children with juvenile idiopathic arthritis, as detected by magnetic resonance imaging but not by ultrasound . Arthritis and Rheumatism , 58 , 1189 – 1196 . Google Scholar CrossRef Search ADS 3. Arvidsson , L.Z. , Smith , H.J. , Flatø , B. and Larheim , T.A . ( 2010 ) Temporomandibular joint findings in adults with long-standing juvenile idiopathic arthritis: CT and MR imaging assessment . Radiology , 256 , 191 – 200 . Google Scholar CrossRef Search ADS 4. Küseler , A. , Pedersen , T.K. , Gelineck , J. and Herlin , T . ( 2005 ) A 2 year followup study of enhanced magnetic resonance imaging and clinical examination of the temporomandibular joint in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 32 , 162 – 169 . 5. Isola , G. , Ramaglia , L. , Cordasco , G. , Lucchese , A. , Fiorillo , L. and Matarese , G . ( 2017 ) The effect of a functional appliance in the management of temporomandibular joint disorders in patients with juvenile idiopathic arthritis . Minerva Stomatologica , 66 , 1 – 8 . 6. Müller , L. , Kellenberger , C.J. , Cannizzaro , E. , Ettlin , D. , Schraner , T. , Bolt , I.B. , Peltomäki , T. and Saurenmann , R.K . ( 2009 ) Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging . Rheumatology (Oxford, England) , 48 , 680 – 685 . Google Scholar CrossRef Search ADS 7. Huntjens , E. , Kiss , G. , Wouters , C. and Carels , C . ( 2008 ) Condylar asymmetry in children with juvenile idiopathic arthritis assessed by cone-beam computed tomography . European Journal of Orthodontics , 30 , 545 – 551 . Google Scholar CrossRef Search ADS 8. Fjeld , M. , Arvidsson , L. , Smith , H.J. , Flatø , B. , Ogaard , B. and Larheim , T . ( 2010 ) Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood . Pediatric Rheumatology Online Journal , 8 , 13 . Google Scholar CrossRef Search ADS 9. Matarese , G. , Isola , G. , Alibrandi , A. , Lo Gullo , A. , Bagnato , G. , Cordasco , G. and Perillo , L . ( 2016 ) Occlusal and MRI characterizations in systemic sclerosis patients: A prospective study from Southern Italian cohort . Joint, Bone, Spine: Revue du Rhumatisme , 83 , 57 – 62 . Google Scholar CrossRef Search ADS 10. Engström , A.L. , Wänman , A. , Johansson , A. , Keshishian , P. and Forsberg , M . ( 2007 ) Juvenile arthritis and development of symptoms of temporomandibular disorders: a 15-year prospective cohort study . Journal of Orofacial Pain , 21 , 120 – 126 . 11. Bakke , M. , Zak , M. , Jensen , B.L. , Pedersen , F.K. and Kreiborg , S . ( 2001 ) Orofacial pain, jaw function, and temporomandibular disorders in women with a history of juvenile chronic arthritis or persistent juvenile chronic arthritis . Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics , 92 , 406 – 414 . Google Scholar CrossRef Search ADS 12. Twilt , M. , Mobers , S.M. , Arends , L.R. , ten Cate , R. and van Suijlekom-Smit , L . ( 2004 ) Temporomandibular involvement in juvenile idiopathic arthritis . The Journal of Rheumatology , 31 , 1418 – 1422 . 13. Oliveira , S. et al. ; Pediatric Rheumatology International Trials Organization (PRINTO) . ( 2007 ) Proxy-reported health-related quality of life of patients with juvenile idiopathic arthritis: the Pediatric Rheumatology International Trials Organization multinational quality of life cohort study . Arthritis and Rheumatism , 57 , 35 – 43 . Google Scholar CrossRef Search ADS 14. Bruns , A. , Hilário , M.O. , Jennings , F. , Silva , C.A. and Natour , J . ( 2008 ) Quality of life and impact of the disease on primary caregivers of juvenile idiopathic arthritis patients . Joint, Bone, Spine: Revue Du Rhumatisme , 75 , 149 – 154 . Google Scholar CrossRef Search ADS 15. Leksell , E. , Ernberg , M. , Magnusson , B. and Hedenberg-Magnusson , B . ( 2012 ) Orofacial pain and dysfunction in children with juvenile idiopathic arthritis: a case-control study . Scandinavian Journal of Rheumatology , 41 , 375 – 378 . Google Scholar CrossRef Search ADS 16. Ahola , K. , Saarinen , A. , Kuuliala , A. , Leirisalo-Repo , M. , Murtomaa , H. and Meurman , J.H . ( 2015 ) Impact of rheumatic diseases on oral health and quality of life . Oral Diseases , 21 , 342 – 348 . Google Scholar CrossRef Search ADS 17. Tollisen , A. , Selvaag , A.M. , Aulie , H.A. , Lilleby , V. , Aasland , A. , Lerdal , A. and Flatø , B . ( 2018 ) Physical functioning, pain and health-related quality of life in adults with juvenile idiopathic arthritis: A longitudinal 30-year follow-up study . Arthritis Care and Research (Hoboken) , 70, 741 – 749 . 18. Jokovic , A. , Locker , D. , Stephens , M. , Kenny , D. , Tompson , B. and Guyatt , G . ( 2002 ) Validity and reliability of a questionnaire for measuring child oral-health-related quality of life . Journal of Dental Research , 81 , 459 – 463 . Google Scholar CrossRef Search ADS 19. Gherunpong , S. , Tsakos , G. and Sheiham , A . ( 2004 ) Developing and evaluating an oral health-related quality of life index for children; the CHILD-OIDP . Community Dental Health , 21 , 161 – 169 . 20. Carle , A.C. , Dewitt , E.M. and Seid , M . ( 2011 ) Measures of health status and quality of life in juvenile rheumatoid arthritis: Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module 3.0, Juvenile Arthritis Quality of Life Questionnaire (JAQQ), Paediatric Rheumatology Quality of Life Scale (PRQL), and Childhood Arthritis Health Profile (CAHP) . Arthritis Care & Research , 63 ( Suppl 11 ), S438 – S445 . Google Scholar CrossRef Search ADS 21. Ruperto , N. , Ravelli , A. , Pistorio , A. , Malattia , C. , Cavuto , S. , Gado-West , L. , Tortorelli , A. , Landgraf , J.M. , Singh , G. and Martini , A .; Paediatric Rheumatology International Trials Organisation . ( 2001 ) Cross-cultural adaptation and psychometric evaluation of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ) in 32 countries. Review of the general methodology . Clinical and Experimental Rheumatology , 19 , S1 – S9 . 22. Frid , P. et al. ; Paediatric Rheumatology International Trials Organisation . ( 2017 ) Temporomandibular joint involvement in association with quality of life, disability, and high disease activity in juvenile idiopathic arthritis . Arthritis Care & Research , 69 , 677 – 686 . Google Scholar CrossRef Search ADS 23. Barbosa , T.d.e.S. , Tureli , M.C. , Nobre-dos-Santos , M. , Puppin-Rontani , R.M. and Gavião , M.B . ( 2013 ) The relationship between oral conditions, masticatory performance and oral health-related quality of life in children . Archives of Oral Biology , 58 , 1070 – 1077 . Google Scholar CrossRef Search ADS 24. Paula , J.S. , Meneghim , M.C. , Pereira , A.C. and Mialhe , F.L . ( 2015 ) Oral health, socio-economic and home environmental factors associated with general and oral-health related quality of life and convergent validity of two instruments . BMC Oral Health , 15 , 26 . Google Scholar CrossRef Search ADS 25. Cassidy , J.T. , Petty , R.E. , Laxer , R. and Lindsley , C . ( 2011 ) Textbook of pediatric rheumatology , 6th ed . Saunders , Philadelphia , pp. 71 – 304 . 26. Sheppard , I.M. and Sheppard , S.M . ( 1965 ) Maximal incisal opening–a diagnostic index ? The Journal of Dental Medicine , 20 , 13 – 15 . 27. Koos , B. , Twilt , M. , Kyank , U. , Fischer-Brandies , H. , Gassling , V. and Tzaribachev , N . ( 2014 ) Reliability of clinical symptoms in diagnosing temporomandibular joint arthritis in juvenile idiopathic arthritis . The Journal of Rheumatology , 41 , 1871 – 1877 . Google Scholar CrossRef Search ADS 28. Cannizzaro , E. , Schroeder , S. , Müller , L.M. , Kellenberger , C.J. and Saurenmann , R.K . ( 2011 ) Temporomandibular joint involvement in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 38 , 510 – 515 . Google Scholar CrossRef Search ADS 29. Kirkhus , E. , Arvidsson , L.Z. , Smith , H.J. , Flatø , B. , Hetlevik , S.O. and Larheim , T.A . ( 2016 ) Disk abnormality coexists with any degree of synovial and osseous abnormality in the temporomandibular joints of children with juvenile idiopathic arthritis . Pediatric Radiology , 46 , 331 – 341 . Google Scholar CrossRef Search ADS 30. Raucci , G. , Pachêco-Pereira , C. , Grassia , V. , d’Apuzzo , F. , Flores-Mir , C. and Perillo , L . ( 2015 ) Maxillary arch changes with transpalatal arch treatment followed by full fixed appliances . The Angle Orthodontist , 85 , 683 – 689 . Google Scholar CrossRef Search ADS 31. Hsieh , Y.J. , Darvann , T.A. , Hermann , N.V. , Larsen , P. , Liao , Y.F. , Bjoern-Joergensen , J. and Kreiborg , S . ( 2016 ) Facial morphology in children and adolescents with juvenile idiopathic arthritis and moderate to severe temporomandibular joint involvement . American Journal of Orthodontics and Dentofacial Orthopedics , 149 , 182 – 191 . Google Scholar CrossRef Search ADS 32. Isola , G. , Anastasi , G.P. , Matarese , G. , Williams , R.C. , Cutroneo , G. , Bracco , P. and Piancino , M.G . ( 2017 ) Functional and molecular outcomes of the human masticatory muscles . Oral Diseases , 1 – 14 . doi: 10.1111/odi.12806. [Epub ahead of print.] 33. Präger , T.M. , Meyer , P. , Rafayelyan , S. , Minden , K. and Jost-Brinkmann , P.G . ( 2015 ) Effect of methotrexate on the mandibular development of arthritic rabbits . European Journal of Orthodontics , 37 , 514 – 521 . Google Scholar CrossRef Search ADS 34. Moretti , C. , Viola , S. , Pistorio , A. , Magni-Manzoni , S. , Ruperto , N. , Martini , A. and Ravelli , A . ( 2005 ) Relative responsiveness of condition specific and generic health status measures in juvenile idiopathic arthritis . Annals of the Rheumatic Diseases , 64 , 257 – 261 . Google Scholar CrossRef Search ADS 35. Pedersen , T.K. , Küseler , A. , Gelineck , J. and Herlin , T . ( 2008 ) A prospective study of magnetic resonance and radiographic imaging in relation to symptoms and clinical findings of the temporomandibular joint in children with juvenile idiopathic arthritis . The Journal of Rheumatology , 35 , 1668 – 1675 . 36. Jokovic , A. , Locker , D. , Tompson , B. and Guyatt , G . ( 2004 ) Questionnaire for measuring oral health-related quality of life in eight- to ten-year-old children . Pediatric Dentistry , 26 , 512 – 518 . 37. Barbosa , T.S. , Gavião , M.B. , Leme , M.S. and Castelo , P.M . ( 2016 ) Oral Health-related Quality of Life in Children and Preadolescents with Caries, Malocclusions or Temporomandibular Disorders . Oral Health & Preventive Dentistry , 14 , 389 . 38. Ostile , I.L. , Johansson , I. , Aasland , A. , Flatö , B. and Möller , A . ( 2010 ) Self-rated physical and psychosocial health in a cohort of young adults with juvenile idiopathic arthritis . Scandinavian Journal of Rheumatology , 39 , 318 – 325 . Google Scholar CrossRef Search ADS 39. Isola , G. , Matarese , G. , Cordasco , G. , Perillo , L. and Ramaglia , L . ( 2016 ) Mechanobiology of the tooth movement during the orthodontic treatment: a literature review . Minerva Stomatologica , 65 , 299 – 327 . 40. Peltomäki , T. , Kreiborg , S. , Pedersen , T.K. , Ogaard , B. and Welbury , R.R . ( 2015 ) Craniofacial growth and dento-alveolar development in juvenile idiopathic arthritis patients . Seminars in Orthodontics , 21 , 84 – 93 . Google Scholar CrossRef Search ADS 41. Cavuoti , S. , Matarese , G. , Isola , G. , Abdolreza , J. , Femiano , F. and Perillo , L . ( 2016 ) Combined orthodontic-surgical management of a transmigrated mandibular canine . The Angle Orthodontist , 86 , 681 – 691 . Google Scholar CrossRef Search ADS 42. Stoustrup , P. , Küseler , A. , Kristensen , K.D. , Herlin , T. and Pedersen , T.K . ( 2013 ) Orthopaedic splint treatment can reduce mandibular asymmetry caused by unilateral temporomandibular involvement in juvenile idiopathic arthritis . European Journal of Orthodontics , 35 , 191 – 198 . Google Scholar CrossRef Search ADS 43. Piancino , M.G. , Cannavale , R. , Dalmasso , P. , Tonni , I. , Filipello , F. , Perillo , L. , Cattalini , M. and Meini , A . ( 2015 ) Condylar asymmetry in patients with juvenile idiopathic arthritis: Could it be a sign of a possible temporomandibular joints involvement ? Seminars in Arthritis and Rheumatism , 45 , 208 – 213 . Google Scholar CrossRef Search ADS 44. Isola , G. , Matarese , G. , Cordasco , G. , Rotondo , F. , Crupi , A. and Ramaglia , L . ( 2015 ) Anticoagulant therapy in patients undergoing dental interventions: a critical review of the literature and current perspectives . Minerva Stomatologica , 64 , 21 – 46 . 45. Stoustrup , P. et al. ; euroTMjoint Research Network . ( 2017 ) Clinical Orofacial Examination in Juvenile Idiopathic Arthritis: International Consensus-based Recommendations for Monitoring Patients in Clinical Practice and Research Studies . The Journal of Rheumatology , 44 , 326 – 333 . Google Scholar CrossRef Search ADS 46. Kristensen , K.D. , Stoustrup , P. , Küseler , A. , Pedersen , T.K. , Twilt , M. and Herlin , T . ( 2016 ) Clinical predictors of temporomandibular joint arthritis in juvenile idiopathic arthritis: A systematic literature review . Seminars in Arthritis and Rheumatism , 45 , 717 – 732 . Google Scholar CrossRef Search ADS 47. Ferlazzo , N. , Currò , M. , Zinellu , A. , Caccamo , D. , Isola , G. , Ventura , V. , Carru , C. , Matarese , G. and Ientile , R . ( 2017 ) Influence of MTHFR genetic background on p16 and MGMT methylation in oral squamous cell cancer . International Journal of Molecular Sciences , 29 , 18 . pii: E724. 48. Twilt , M. , Schulten , A.J. , Verschure , F. , Wisse , L. , Prahl-Andersen , B. and van Suijlekom-Smit , L.W . ( 2008 ) Long-term followup of temporomandibular joint involvement in juvenile idiopathic arthritis . Arthritis and Rheumatism , 59 , 546 – 552 . Google Scholar CrossRef Search ADS 49. Stoustrup , P.B. , Ahlefeldt-Laurvig-Lehn , N. , Kristensen , K.D. , Arvidsson , L.Z. , Twilt , M. , Cattaneo , P.M. , Küseler , A. , Christensen , A.E. , Herlin , T. and Pedersen , T.K . ( 2018 ) No association between types of unilateral mandibular condylar abnormalities and facial asymmetry in orthopedic-treated patients with juvenile idiopathic arthritis . American Journal of Orthodontics and Dentofacial Orthopedics , 153 , 214 – 223 . Google Scholar CrossRef Search ADS © The Author(s) 2018. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/about_us/legal/notices)

Journal

The European Journal of OrthodonticsOxford University Press

Published: Jun 6, 2018

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off