EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice.

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Evaluation of MR imaging guided steroid injection of the sacroiliac joints for the treatment of children with refractory enthesitis-related arthritis.

OBJECTIVES: To test the hypothesis that MR imaging guided triamcinolone acetonide injection into the sacroiliac joints of children with enthesitis-related arthritis is feasible, accurate and safe; and effectively reduces sacroiliac inflammation and disease progression. METHODS: A retrospective analysis of 14 children (6/14 [43%] female, 8/14 (57%) male; mean age, 13.2 years; range, 6-16 years) who received MR imaging guided sacroiliac joint injections at 0.2 Tesla or 1.5 Tesla for enthesitis-related arthritis and acute sacroilitis refractory to medical therapy was performed. 20 mg triamcinolone acetonide were injected. Assessed were intra-articular drug delivery; image quality, duration, and complications. Success of therapy was defined by change of sacroiliac inflammation. Remission time and erosions were assessed by follow-up MRI (range, 10-22 months). RESULTS: Twenty four procedures resulted in intra-articular injection. Image quality was sufficient. No complications occurred. Procedure time was 40 min. Sedation time was 22 min. Success of therapy was achieved in 11/14 (79%) children. Sacroiliac inflammation decreased significantly (-59%). Median remission time was 13.7 months. No erosions occurred. CONCLUSIONS: MR imaging guided steroid injection of the sacroiliac joints is feasible, accurate, and safe and can effectively reduce sacroiliac inflammatory activity and may therefore aid in the prevention of disease progression.

[Interdisciplinary treatment of temporomandibular inflammation in children with juvenile idiopathic arthritis]. / Interdisziplinäre Therapie der Kiefergelenkentzündung bei Kindern mit juveniler idiopathischer Arthritis.

Involvement of the temporomandibular joints in children with juvenile idiopathic arthritis usually leads to destruction of the mandibular condyles with consistent growth disturbances and facial anomalies. Due to its frequently silent course, temporomandibular arthritis tends to be a diagnostic and therapeutic challenge. In addition to drug therapy, orthodontics and physiotherapy are essential to prevent further progression and restore lost temporomandibular function.

[Juvenile idiopathic arthritis: the silent killer of pediatric temporomandibular joints]. / Juvenile idiopathische Arthritis: Der leise Zerstörer kindlicher Kiefergelenke.

Temporomandibular joint involvement occurs in up to 87% of the children with juvenile idiopathic with half of the patients being asymptomatic. In these cases the only option to diagnose arthritis of the temporomandibular joints is the gadolinium enhanced magnetic resonance imaging. Therapeutic approaches include drugs, orthodontic and physiotherapeutic management, although only scant data on the effectiveness of these treatments are available. Several reports in recent years have pointed to imaging guided intraarticular steroids as efficient treatment.

Spectrum of magnetic resonance imaging appearances of juvenile temporomandibular joints (TMJ) in non-rheumatic children.

BACKGROUND: Temporomandibular joints (TMJ) are frequently involved in children with juvenile idiopathic arthritis (JIA), and gadolinium-enhanced magnetic resonance imaging (MRI) is the only modality for an early diagnosis. However, only very few data exist on the appearance of contrast-enhanced MRI of normal juvenile TMJ. PURPOSE: To define the spectrum of normal MRI findings of juvenile TMJ, and to assess a possible overlap with findings typical for active synovitis in JIA. MATERIAL AND METHODS: 96 children (192 TMJ), 51 boys and 45 girls with a median age of 7.8 years (range 3-13 years), underwent a head MRI. The presence of autoimmune disease, including JIA, was excluded via chart history, available laboratory findings, and the absence of known typical pathological MRI changes (degree of synovial enhancement, hyperintense signal on T2-weighted images in the synovia or bone marrow, and morphologic changes of the mandibular condyle) of the TMJ affected by JIA. RESULTS: In 90 (94%) children, the TMJ showed no MRI abnormalities compatible with arthritis. In three children (3%), the only abnormal MRI finding was a small bilateral joint effusion. A further three children (3%) had a mild synovial enhancement seen on both axial and coronal MR planes in one child and only in the axial plane in the other two children. Signal hyperintensity on T2-weighted images and other corresponding characteristics of TMJ inflammation were lacking in all these six patients. CONCLUSION: The vast majority of juvenile TMJ in non-rheumatic children shows no MRI abnormalities. Exceptions, including a discrete enhancement of the synovial membrane (3%) or small joint effusions (3%), can occur in a minority of patients, but none of them are accompanied by other signs of inflammation or morphological changes of the TMJ.

Comparison of imaging techniques in the diagnosis of bridging bronchus.

Bridging bronchus (BB) is a rare, congenital bronchial anomaly that is frequently associated with congenital cardiac malformations, especially left pulmonary artery sling. It represents an anomalous bronchus to the right originating from the left main bronchus. Discrimination from other bronchial anomalies is important, since BB is frequently associated with bronchial stenoses due to abnormal cartilage rings. This case study describes the findings of bronchoscopy, bronchography and multidetector computed tomography (MDCT) in three patients. Bronchoscopy was helpful in the description of the severity and length of bronchial stenoses. However, it was not possible to establish a diagnosis of BB based on this method in two patients, since it is difficult or even impossible to differentiate the bifurcation from the pseudocarina. It was not possible to establish the correct diagnosis in all patients based on bronchography or MDCT. MDCT was able to depict the relationship of bronchial and vascular structures, which is particularly important in patients with pulmonary artery sling. Multidetector computed tomography is preferable to bronchography as it is less invasive and due to its short acquisition time it can be performed in children with severe respiratory disease. In the current authors' experience, detection of cartilage rings still requires flexible bronchoscopy.

Interferon-alpha--a new therapeutic option in refractory juvenile Behçet's disease with CNS involvement.

OBJECTIVE: To report the successful treatment with recombinant human IFN- alpha 2a (rhIFN-alpha2a) in two male adolescents suffering from severe treatment-resistant Behçet's disease (BD) with central nervous system (CNS) involvement. METHODS: The patients were 14- and 15-yrs old. Both met the International Study Group for Behçet's disease, O'Duffy and the Japanese criteria for the classification or diagnosis of BD. Signs of CNS involvement were impaired sensorimotor function of the left arm, hemiparesis of right arm and leg, dizziness and walking instability in Patient 1, weakness of both legs, impaired bladder-, bowel- and sexual function in Patient 2 and vasculitic lesions on cranial MRI in both patients. RhIFN-alpha2a was administered initially at 3 million IU/day for 4 weeks followed by 3 x 3 million IU/week. RESULTS: Complete remission was achieved in Patient 1 (reduction in BD activity score from 17 to 2). Patient 2 experienced remarkable improvement (reduction of BD activity score from 23 to 15). In both patients the MRI lesions improved. Patient 2 had mild flu-like symptoms as adverse effect. CONCLUSION: RhIFN-alpha2a was effective and well tolerated in these juvenile patients with severe neurological BD. Regarding the serious consequences following ocular and CNS affection and adverse effects of steroid dependency, administration of rhIFN-alpha2a at an earlier time point needs to be considered.

Amendment of the OMERACT ultrasound definitions of joints' features in healthy children when using the DOPPLER technique.

BACKGROUND: Recently preliminary ultrasonography (US) definitions, in B mode, for normal components of pediatric joints have been developed by the OMERACT US group. The aim of the current study was to include Doppler findings in the evaluation and definition of normal joint features that can be visualized in healthy children at different age groups. METHODS: A multistep approach was used. Firstly, new additional definitions of joint components were proposed during an expert meeting. In the second step, these definitions, along with the preliminary B-mode-US definitions, were tested for feasibility in an exercise in healthy children at different age groups. In the last step, a larger panel of US experts were invited to join a web-based consensus process in order to approve the developed definitions using the Delphi methodology. A Likert scale of 1-5 was used to assess agreement. RESULTS: Physiological vascularity and fat pad tissue were identified and tested as two additional joint components in healthy children. Since physiological vascularity changes over the time in the growing skeleton, the final definition of Doppler findings comprised separate statements instead of a single full definition. A total of seven statements was developed and included in a written Delphi questionnaire to define and validate the new components. The final definitions for fat pad and physiological vascularity agreed by the group of experts reached 92.9% and 100% agreement respectively in a web survey. CONCLUSION: The inclusion of these two additional joints components which are linked to detection of Doppler signal in pediatric healthy joints will improve the identification of abnormalities in children with joint pathologies.

Juvenile idiopathic arthritis and the temporomandibular joint: A comprehensive review.

Juvenile idiopathic arthritis is the most common inflammatory rheumatic disease of childhood and represents a series of chronic inflammatory arthritides of unknown cause. Involvement of the temporomandibular joint has been reported in up to 87% of children with juvenile idiopathic arthritis when based on magnetic tomography imaging; it can be asymptomatic and may lead to severe long term complications. In this review a summary of the contemporary literature of imaging of the temporomandibular joint in children with juvenile idiopathic arthritis will be provided, including ultrasound which is a valuable method for guided joint injections, but does not necessarily allow detection of acute inflammation, cone beam computed tomography, which has emerged as a feasible and accurate low-dose alternative as compared to conventional computed tomography to detect destructive change, and magnetic resonance imaging which is considered the method of choice for assessing acute, inflammatory change, although the lack of normative standards remains a challenge in children.

Pathological changes in the TMJ and the length of the ramus in patients with confirmed juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is characterized by a progressive destruction of the joints. The temporomandibular joints (TMJ) are especially likely to be affected. The often undetected arthritis in the TMJ in particular can cause significant destruction and craniofacial developmental abnormalities. The aim of this study was to analyze the destructive impact of JIA on TMJ and mandibular development. MATERIAL AND METHODS: We analyzed a total of 92 joints and mandibular rami using digital cone-beam tomography (CBT) and compared 23 consecutively treated JIA patients with 23 healthy controls, matched for age and gender. We evaluated ramus length, vertical depth of the articular fossa, anterior-posterior dimensions of the mandibular head and condylar process. The statistical analysis was performed using non-parametric Wilcoxon and Kruskal-Wallis Rank Sum tests. RESULTS: The JIA patients exhibited significantly more pronounced asymmetries. However, we were unable to detect significant differences in the metric measuring distances. The different JIA subtypes exerted no statistically significant influence. CONCLUSIONS: The possible destruction arising as a result of JIA concerns the TMJ and the length of the mandibular ramus. These craniofacial anomalies demonstrate the central importance of sufficiently early detection and timely treatment in the prevention of such growth disturbances.

Classification of temporomandibular joint erosion, arthritis, and inflammation in patients with juvenile idiopathic arthritis.

INTRODUCTION: Juvenile idiopathic arthritis is the most common disease in pediatric rheumatology. It is characterized by chronically progressive joint destruction. The temporomandibular joints (TMJs) are involved in up to 87% of patients and may take an asymptomatic course in 69% of cases. Other than contrast-enhanced magnetic resonance imaging (MRI), there are no reliable screening symptoms or non-invasive procedures available to diagnose the inflammation in its acute form. The goal of this study was to establish an imaging-based classification system for TMJ erosion via MRI and cone-beam computed tomography (CBCT) in an effort to improve indication-specific treatment approaches and to facilitate the comparison of findings. MATERIALS AND METHODS: A total of 46 patients were included. Contrast-enhanced MRI and CBCT images obtained during treatment by pediatric rheumatologists and orthodontists were available from 23 patients with juvenile idiopathic arthritis. We devised a classification system combining the findings of both imaging techniques based on this patient sample in comparison with CBCT findings from an age- and gender-matched group of 23 non-arthritis patients, taking into consideration the available literature and administration of contrast medium. RESULTS: Our cohort of 46 patients comprised 60% female and 40% male patients with a mean age of 14 years, providing a total of 92 TMJs for evaluation. We were able to apply the findings efficiently and conveniently to this classification system with no relevant interobserver differences. Mild structural abnormalities were noted in 21% of TMJs in the control group, whereas 83% of TMJs in the arthritis group exhibited severe anomalies, including cases of extreme destruction. Age and gender did not affect the degree of destruction significantly. CONCLUSION: This is the first classification system to link CBCT and MRI with the use of contrast medium. Contrast-enhanced MRI is an internationally recognized technique that permits acute inflammation to be unequivocally diagnosed. Although structural erosion of the TMJs in our arthritis group was generally severe and significant, we were surprised to observe some cases that were clinically asymptomatic.

Predictors of delayed referral to a pediatric rheumatology center.

OBJECTIVE: To report on referral patterns of primary physicians for children subsequently diagnosed with juvenile idiopathic arthritis (JIA) and to identify predictors of delayed referral to a pediatric rheumatology center. METHODS: A retrospective cohort study of consecutive patients with JIA referred to a pediatric rheumatology center over a 15-year period was performed. Variables included age, sex, JIA subtype, the physician's subspecialty, and distance to the pediatric rheumatology center. Outcome parameters were the time to first presentation to a primary physician, the time to the first rheumatology visit, and the total time to referral. Putative predictors were evaluated by analysis of variance, resulting in regression models. RESULTS: A total of 132 patients with JIA were included; 83 (63%) were female. The median age at the onset of symptoms was 4.5 years (range 1.0-15.8 years). Most frequently, children were referred by pediatricians (49.4%) or orthopedic surgeons (34.1%). The median time to first presentation was short at 10 days (range 0-1,610 days). In contrast, the median time to first rheumatology visit was 60 days (range 0.0-2,100.0 days), resulting in a long median total time to referral of 90 days (range 0.0-2,160.0 days). Statistically significant predictors for delayed referral were the primary physician's subspecialty (P = 0.016) and the distance to the pediatric rheumatology center (P = 0.001). Children living in remote areas or referred by orthopedic surgeons had the longest referral times. CONCLUSION: Despite free access to health care in Germany, children with JIA are referred to pediatric rheumatology centers with significant delay. Educational interventions targeting primary physicians and orthopedic surgeons may contribute to earlier referral to pediatric rheumatology centers and improve outcome in patients with JIA.

Safety and efficacy of etanercept in children with juvenile idiopathic arthritis below the age of 4 years.

Little is known about the safety and efficacy of etanercept in children below the age of 4 years. Twenty-five patients with juvenile idiopathic arthritis (JIA) below the age of 4 years, who received etanercept, were documented in the German JIA Etanercept Registry. Patients with the nonsystemic JIA disease-subtype responded more frequently to treatment with etanercept than systemic onset patients. At last observation, two (20%) of the nonsystemic patients did not reach a PedACR 30 response, while six (40%) of the systemic onset patients did not respond to the therapy. Complete resolution of symptoms was observed in two (20%) nonsystemic and in five (33%) systemic onset patients with JIA. Tolerability was good with only two infections occurring in the total patients group. Patients with JIA below the age of 4 years, with a methotrexate-resistant disease course, would also benefit from treatment with etanercept, showing a good tolerability. The restriction to children older than 4 years appears to be artificial without any good rationale.

Musculoskeletal abnormalities in juvenile idiopathic arthritis--a 4-year longitudinal study.

OBJECTIVES: Bone density in juvenile idiopathic arthritis (JIA) is largely normal whereas geometric parameters of bone are abnormal. The most prominent changes are a reduction in muscle cross sectional area (CSA) and muscle force. The aim of this study was to assess the evolution of these changes throughout the course of the disease. METHODS: Twenty-five JIA patients were assessed by peripheral quantitative computed tomography longitudinally with a median of 48 months between measurements. At the non-dominant forearm, parameters of bone density and geometry as well as muscle CSA were recorded. The strength-strain index (SSI) as an indicator of bone strength was determined. RESULTS: Muscle CSA improved from a median Z-score of -1.94 to -1.10 at follow-up. Cortical thickness increased from -1.55 to -0.97 whereas marrow area remained enlarged at 0.96 vs 1.05. Cortical density remained normal at 0.34 vs 0.69 and trabecular density improved from -0.75 to -0.36. The SSI increased from -0.79 to -0.13. CONCLUSIONS: JIA patients show some improvement in muscle CSA and an increase in cortical thickness. The marrow area remains enlarged but by increasing the cortical thickness, area and diameter, bone strength increases. These geometric adaptations, for the first time shown in this study, nevertheless represent a disturbance in skeletal development. In addition to efficient disease control, training modalities to improve muscle strength and subsequent bone development have to be included in therapeutic approaches.

Development of granulomatous common variable immunodeficiency subsequent to infection with Toxoplasma gondii.

Common variable immunodeficiency (CVID) is a heterogeneous immunodeficiency that is accompanied by granulomatous lesions in 5-10% of cases. Why some patients develop granulomatous disease remains unclear. Here we describe a 12-year-old previously healthy girl who presented with pancytopenia and granulomatous lymphoproliferation subsequent to infection with Toxoplasma gondii. Loosely arranged non-fibrosing granulomas were observed in the liver, lymph nodes and lung, but no Toxoplasma tachyzoites could be demonstrated and polymerase chain reaction (PCR) and culture were negative for Toxoplasma and a wide range of other pathogens. While the patient had a normal peripheral B cell status at presentation, the development of CVID could be observed during the following months, leading to a loss of memory B cells. This was accompanied by an increasingly activated CD4(+) T cell compartment and high serum levels of angiotensin-converting enzyme (ACE), tumour necrosis factor (TNF) and sCD25. Steroid therapy reduced pancytopenia, granulomatous lymphoproliferation and cytokine elevations, but did not improve the B cell status. This is the first report of an association of Toxoplasma infection with granulomatous CVID and provides one of the rare examples where the onset of CVID could be documented subsequent to an infectious disease.