Accepted Manuscript Juvenile idiopathic arthritis and the Temporomandibular joint: a comprehensive review S. El Assar de la Fuente, O. Angenete, S. Jellestad, N. Tzaribachev, B. Koos, K. Rosendahl PII:

S1010-5182(16)00028-7

DOI:

10.1016/j.jcms.2016.01.014

Reference:

YJCMS 2286

To appear in:

Journal of Cranio-Maxillo-Facial Surgery

Received Date: 9 July 2015 Revised Date:

12 December 2015

Accepted Date: 26 January 2016

Please cite this article as: El Assar de la Fuente S, Angenete O, Jellestad S, Tzaribachev N, Koos B, Rosendahl K, Juvenile idiopathic arthritis and the Temporomandibular joint: a comprehensive review, Journal of Cranio-Maxillofacial Surgery (2016), doi: 10.1016/j.jcms.2016.01.014. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Juvenile idiopathic arthritis and the Temporomandibular joint: a comprehensive review.

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El Assar de la Fuente S1, Angenete O2, Jellestad S3,Tzaribachev4 N, Koos B5, Rosendahl K3, 6

1. Department of Radiology, Dr. Negrin Hospital, Las Palmas de Gran Canaria, Spain. 2. Department of Radiology, St Olav University Hospital, Norway.

3. Department of Radiology, Haukeland University Hospital, Bergen, Norway.

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4. Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany. 5. Department of Orthodontics, University of Rostock, Germany.

Conflict of interest statement

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6. University of Bergen, Department of Clinical Medicine K1, Norway.

The authors have declared no conflicts of interest. Role of the funding source

Correspondance to:

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The present study was financed internally by the author’s institution.

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Karen Rosendahl Consultant Paediatric Radiologist / Professor Email: [email protected]

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Haukeland University Hospital / University of Bergen Jonas Lies vei 65, 5021 Bergen, Norway Tel: +47 55975221; Fax:+47 55975897

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Abstract Juvenile idiopathic arthritis the most common inflammatory rheumatic disease of

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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

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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

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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

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method of choice for assessing acute, inflammatory change, although the lack of

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Keywords

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normative standards remains a challenge in children.

Temporomandibular Joint, Juvenile Idiopathic Arthritis, Review, Imaging, MRI, Ultrasound

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Article 1. Introduction

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Juvenile idiopathic arthritis (JIA) represents a series of chronic inflammatory arthritides that develop before the age of 16 years, persist for at least 6 weeks, have no identifiable cause and are meant to be distinct from adult rheumatoid arthritis (Gabriel et al., 2009;

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Kaipiainen-Seppanen et al., 2001; Symmons et al., 1996). Its cause remains unknown despite research on potential predisposing mechanisms such as infection, trauma,

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psychological factors, heredity, familiar influences, and a host of immunologic phenomena (Calabro, 1986, Calabro, 1976).With an annual incidence ranging from 8 to 22.6 per 100 000 children, a prevalence of 7–401 per 100 000 children depending on different regions (Berntson et al., 2003) and affecting 1 in 1000 children worldwide

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(Schneider et al., 2002), JIA is the most common inflammatory rheumatic disease of childhood (Gewanter et al., 1983). It has been grouped into seven different subtypes based on clinical and laboratory features such as family history, number of joints affected

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in a period of 6 months, systemic involvement (hepato-splenomgaly or serositis), the presence of psoriasis, anterior uveitis or sacroiliac joint tenderness, Rheumatoid Factor+

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and HLA B27 +/- (International League of Associations for Rheumatology (ILAR) (Petty et al., 2004; Ravelli et al., 2011)(Table 1). The temporomandibular joint (TMJ), formerly known as “the forgotten joint” (Arabshahi et al., 2006) is involved in around half of the children with JIA, ranging from 17-87% depending on subtype, diagnostic criteria used and ethnicity (Arabshahi et al., 2006; Cannizzaro et al., 2011; Jank et al., 2007; Kuseler et al., 1998; Pedersen et al., 2001;

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Ringold et al., 2009; Twilt et al., 2006; Weiss et al., 2008). Bilateral affection occurs in 53% (Weiss et al., 2008) to 83% of the cases (Twilt et al., 2006), and the rate tends to increase over time (Arvidsson et al., 2010). Time from onset of disease until involvement

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of the TMJ’s varies significantly (Scolozzi et al., 2005; Twilt et al., 2006). Although Stoll et al. confirmed previous reports that all children with JIA are at risk of TMJ arthritis (Stoll et al., 2012), it seems that while HLA-B27 positive patients have less risk

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(Pedersen et al., 2001); systemic affection, early onset (95th percentile of healthy aged

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matched controls (=>1,5mm).

Adding a dynamic evaluation has improved US performance as compared to MRI (Jank et al., 2005), however, standardized, US-based definitions for TMJ arthritis in children are still lacking. To address these shortcomings, a pediatric US group within the OMERACT Ultrasound Task Force has been established. Moreover, the EULAR has committed to involve pediatric rheumatologists in future activities on imaging (Lanni et al., 2013).

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In sum, the role of ultrasound in the initial diagnosis of TMJ arthritis is still unclear. However, in the absence of MRI, in advanced stages of the disease and in follow-up of known pathology (Assaf et al., 2013) it may be helpful. At present, its most important

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drugs (Assaf et al., 2013; Parra et al., 2010).

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application is ultrasound guided joint aspiration and instillation of anti-inflammatory

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MRI

The introduction of MRI in the diagnosis of TMJ affection in JIA patients has led to earlier diagnosis and higher rates due to its ability to detect both active and permanent change (Kuseler et al., 2005; Kuseler et al., 1998; Muller et al., 2009; Ringold et al., 2009). Currently, MR is considered a screening tool for early disease detection, even in

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the absence of symptoms (Argyropoulou et al., 2009; Pedersen et al., 2008; Weiss et al., 2008) and particularly in those at risk for TMJ involvement(Pedersen et al., 2008). Several studies have suggested that the use of intravenous contrast medium (gadolinium)

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increases the sensitivity for detecting active inflammation and synovial thickening in the

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TMJs in children with JIA. (Aiken et al., 2012; Kuseler et al., 2005; Kuseler et al., 1998; Stoll et al., 2012). The role of contrast-enhanced MRI in early TMJ arthritis is, however, not clear, and further studies are needed (von Kalle et al., 2014). We have previously shown that definitions of bone marrow-edema, effusions and erosions according to the OMERACT criteria for disease in adults with rheumatoid arthritis does not apply for children’s wrists as a high proportion of healthy 5-15 year olds will exhibit these features (Muller et al., 2011).Different appearances have also been

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found for growing TMJs (Tzaribachev et al., 2009), although most joints show smooth borders of a rather oval or round condyle (Karlo et al., 2010; Tzaribachev et al., 2009; von Kalle et al., 2013) (Figure 6). On T2 images, a minority of healthy children has a

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sliver of joint fluid seen as small, high signal dots/lines within a joint recess (Muller et

al., 2009). In the absence of additional inflammatory markers, this finding is considered

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normal.

Whether or not it is possible to visualize normal synovial enhancement after intravenous

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administration of contrast varies according to techniques and definitions used. As the synovium can be difficult to distinguish from both joint effusion and capsule, some authors have adopted the term “soft tissues of the joint” (von Kalle et al., 2013). In most juvenile TMJs, a mild synovial enhancement can be seen when subjectively comparing pre- and post contrast T1-weighted images (von Kalle et al., 2013). On the other hand,

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when comparing synovial signal intensity with that of muscle tissue on post contrast images, synovial enhancement can be seen in only a minority of healthy TMJs (Abramowicz et al., 2011; Weiss et al., 2008). Von Kalle et al. (von Kalle et al., 2013)

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argued that the latter was an unreliable method as post contrast signal intensity of the

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muscle varied widely. Others suggest that contrast enhancement can be only very rarely detected in normal TMJs (Tzaribachev et al., 2009). In our experience, dynamic subtraction techniques may prove valuable (Figure 7).

4. Discussion MRI findings in JIA associated TMJ-arthritis

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Early features of active arthritis are typically those of joint effusion (Muller et al., 2009) (Figure 8), synovitis and bone marrow edema (Vaid et al., 2014). Joint effusion has been reported the second most common finding ranging from 23% to 65% of patients with JIA

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(Abramowicz et al., 2011; Kuseler et al., 2005). In TMJ arthritis, an effusion can be very subtle initially, and confined to parts of the two separate joint cavities, while in advanced

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disease with severe destruction effusions may be absent (Vaid et al., 2014).

Synovitis defined as a thickened synovium with avid enhancement on early postcontrast

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images can be uni- or bilateral(Meyers et al., 2013) (Figure 9). With progressive inflammation, the synovium can proliferate to form pannus. Pannus is considered a chronic manifestation (Vaid et al., 2014), and is often associated with other permanent features such as erosions/flattened condyle (Figure 8) although Kuseler et al. (Kuseler et al., 2005) found pannus not only in the severely affected joints where a chronic stage has

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been reached, but also in joints with small erosions and vivid enhancement, indicating an earlier stage of TMJ involvement. It seems that synovial inflammatory activity starts rather early in the TMJs after JIA has been diagnosed, and then continues without

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changes in intensity more or less independently from the erosions score which increase

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over time as a sign of a continuing destructive process of the bony structures (Kuseler et al., 2005).

Since fluid-sensitive sequences (T2, STIR and to a lesser extent intermediate weightedPD) cannot reliably differentiate between synovium and joint effusion(Kuseler et al., 2005; Tzaribachev et al., 2009; von Kalle et al., 2013; von et al., 2014), post contrast images have become mandatory in the assessment of acute inflammation (Kuseler et al., 1998; Tzaribachev et al., 2009). Post contrast images may also facilitate the

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differentiation between active synovial inflammation and fibrotic (non-inflamed) pannus (Meyers et al., 2013; Sheybani et al., 2013), thus increasing the sensitivity for active change (Aiken et al., 2012; Kuseler et al., 2005; Kuseler et al., 1998). Post contrast

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images should be performed immediately after intravenous contrast injection; within 5 min(Muller et al., 2009), and not far beyond 8 to10 minutes (Kuseler et al., 2005) to avoid contrast diffusion into the joint space, which limit the differentiation between

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enhancing synovium and adjacent joint fluid, and can mimic true synovial thickening

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(Ostergaard et al., 2001).

Even though some authors suggest that any degree of synovial enhancement in the temporomandibular joint in JIA children is indicative of synovial inflammation (Argyropoulou et al., 2009; Kuseler et al., 2005; Pedersen et al., 2008; Stoll et al., 2012), it seems that the degree of enhancement strongly correlates with the degree of

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pathological articular findings (Kuseler et al., 2005; Kuseler et al., 1998). Its severity correlates with the amount of condylar damage(Muller et al., 2009), and with the maximum mouth opening that might not be only due to irreversible damage (Muller et

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al., 2009) and furthermore, it seems that the severity of synovial inflammation in the TMJ

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demonstrated on MRI is correlated with S100A12 serum marker (calgranulin C) known as “the proinflammatory protein” (Abdul-Aziez et al., 2010).Synovial cysts extending from the adjacent synovial joint have characteristic appearance on MR imaging, and should not be mistaken for synovial effusions (Meyers et al., 2013). MRI is the only modality that can demonstrate bone marrow edema (BME) like changes (Johnson, 2006). Following intravenous contrast BME tends to enhance (Meyers et al., 2013; Vaid et al., 2014), and is therefore thought to reflect true osteitis rather than

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increased water content alone (Ostergaard et al., 2003). BME is considered pre-erosive changes to the condyles (Breton et al., 2012).

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In more advanced stages of TMJ arthritis, morphologic changes, such as a flattened articular eminence (Argyropoulou et al., 2009; Mouterde et al., 2009) and derangement of the condyle (cortical bone thinning, flattening, focal to extensive erosive changes with

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marked destruction and irregularity of the articular surface) can be seen on MRI.

Spoiled Gradient Echo sequences have the advantage of fast pre-contrast T1-weighted

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images and permit dynamic acquisitions performing multiple post contrast phases (von Kalle et al., 2013). Specifically, the T1-3D-FSPGR sequence has proven superior to other sequences in the assessment of mandibular cortical bone of cadaveric specimens using micro-CT as reference (Karlo et al., 2012) which in part may be due to less chemical shift

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and susceptibility artifacts (Reichert et al., 2004). MRI can also detect hypertrophic bone formation (osteophytes) which are best shown by CT in advanced disease (Vaid et al., 2014), as well as heterotopic bone formation which may be associated with persistent

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inflammation, use of intra-articular steroids, or both. These heterotopic bone formations

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seem to be associated with aggressive TMJ arthritis (Ringold et al., 2011). Children with TMJ arthritis may have restricted condylar motion in the open-mouth position, (Argyropoulou et al., 2009)and / or reduced condylar motion at maximally opened mouth (Stabrun et al., 1987). Disc abnormalities usually occur late in the disease, starting with an attenuated and poorly defined disc (Arvidsson et al., 2010). With progression of the disease, the disc can become irregular, extremely attenuated (Meyers et al., 2013; Vaid et al., 2014)flattened (in up to 17% of affected joints) (Argyropoulou et

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al., 2009), no longer recognizable and even displaced(Meyers et al., 2013; Vaid et al., 2014). If displacement occurs, it is usually in an anterior or anteromedial direction (Aiken et al., 2012) with or without capacity of reducibility (Meyers et al., 2013). Usually an

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anteriorly displaced disk is accompanied by other features of JIA. If normal bone tissue and no contrast enhancement are demonstrated, the disc is considered to have internal derangement only (Arvidsson et al., 2010). The problem manifests when disk

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displacement and minor bone abnormalities are found (Arvidsson et al., 2010). Non-

reducing disk displacement may also lead to a deformed condyle, especially in children

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(Farina et al., 2009), and joints with disk displacement and osteoarthritis secondary to this condition may show contrast enhancement (Farina et al., 2009; Yura et al., 2010). To complicate the whole picture, displaced discs can be accompanied by synovial effusion (Adame et al., 1998) thus it may be impossible sometimes to distinguish this pattern in

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non-rheumatic diseased TMJs, from long term findings in JIA involvement, underscoring the value of repeat examinations (Arvidsson et al., 2010). Close and open mouth views using coronal and sagittal images are helpful to document meniscus position and degree

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of reduction (Aiken et al., 2012; Vilanova et al., 2007). If imaging the disc for size and signal characteristics is considered useful, a partial open mouth position facilitates

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visualization of the entire disc as it separates the low signal meniscus from two low signal areas of neighbouring cortex. This can be done by placing a special device that provides increments in mouth from grade 1 to 5. This helps in establishing a cine video imaging that ease appreciation of morphology and abnormalities such as “stuck disc” (Vilanova et al., 2007). Higher magnetic field strengths (3T) provide better image quality, more accurate

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differentiation between normal and inflamed TMJs and better delineation of the cortical bone of the mandibular condyle (Stehling et al., 2007). Introduction of T2 relaxation time cartilage mapping, which helps to detect microstructural changes caused by inflammation

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before morphologic changes can be detected at conventional MR imaging, has been used in cartilage of knee joints and the small joints of the hands (Karmazyn et al.,

2012).Ultrashort time-to-echo (UTE)MRI which quantifies short T2* properties at a high

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signal to noise ratio is a promising technique for TMJs(Sanal et al., 2011). Moreover, Dual-Echo Steady-State Sequence (DESS), a modified fully refocused Steady-State

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sequence provides excellent anatomic details (Chavhan et al., 2008)of non-ossified cartilage in children (Chavhan, 2008). It is a matter of time till these techniques will find their way to the TMJs.

Despite all these qualities, MR imaging is not always available, it is lengthy with a

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current imaging protocol time of approximately 45 minutes (Vaid et al., 2014), they require intravenous administration of contrast and frequently entail sedation (Breton et al., 2012; Vaid et al., 2014) which allows for only closed mouth images (Vaid et al.,

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2014). Currently there is no standardized, validated MRI-based scoring system for acute

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or chronic TMJ arthritis in children.

5. Conclusion

To summarize, TMJ involvement is frequent in JIA, can be asymptomatic and may lead to severe long term complications. To detect destructive change, CBCT has emerged as a feasible and accurate low-dose alternative as compared to CT whilst high-resolution

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contrast-enhanced MRI is the method of choice for assessing acute change. PTG and the lateral cephalogram should be interpreted with caution due to its poor reliability induced by various limitations like superimposition and geometric distorsion. Lack of normative

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standards remains a challenge when defining pathology. Ultrasound is valuable method for guided joint injections, but does not necessarily allow detection of acute

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inflammation.

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References Abdul-Aziez OA, Saber NZ, El-Bakry SA, Mohammad AA, Abdel-Maksud SS, Ali Y:

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Serum S100A12 and temporomandibular joint magnetic resonance imaging in juvenile idiopathic arthritis Egyptian patients: a case control study. Pak J Biol Sci:13(3):10113,2010.

SC

Abramowicz S, Cheon JE, Kim S, Bacic J, Lee EY: Magnetic resonance imaging of

temporomandibular joints in children with arthritis. J Oral Maxillofac Surg:69(9):2321-

M AN U

8,2011.

Adame CG, Monje F, Offnoz M, Martin-Granizo R: Effusion in magnetic resonance imaging of the temporomandibular joint: a study of 123 joints. J Oral Maxillofac

TE D

Surg:56(3):314-8,1998.

Adams GL, Gansky SA, Miller AJ, Harrell WE, Jr., Hatcher DC: Comparison between traditional 2-dimensional cephalometry and a 3-dimensional approach on human dry

EP

skulls. Am J Orthod Dentofacial Orthop:126(4):397-409,2004. Ahlqvist J, Eliasson S, Welander U: The effect of projection errors on cephalometric

AC C

length measurements. Eur J Orthod:8(3):141-8,1986. Ahmad M, Hollender L, Anderson Q, Kartha K, Ohrbach R, Truelove EL et al.: Research diagnostic criteria for temporomandibular disorders (RDC/TMD): development of image analysis criteria and examiner reliability for image analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod:107(6):844-60,2009.

ACCEPTED MANUSCRIPT 24

Aiken A, Bouloux G, Hudgins P: MR imaging of the temporomandibular joint. Magn Reson Imaging Clin N Am:20(3):397-412,2012.

RI PT

Alstergren P, Larsson PT, Kopp S: Successful treatment with multiple intra-articular injections of infliximab in a patient with psoriatic arthritis. Scand J Rheumatol:37(2):1557,2008.

SC

Arabshahi B, Cron RQ: Temporomandibular joint arthritis in juvenile idiopathic arthritis:

M AN U

the forgotten joint. Curr Opin Rheumatol:18(5):490-5,2006.

Argyropoulou MI, Margariti PN, Karali A, Astrakas L, Alfandaki S, Kosta P et al.: Temporomandibular joint involvement in juvenile idiopathic arthritis: clinical predictors of magnetic resonance imaging signs. Eur Radiol:19(3):693-700,2009.

TE D

Arvidsson LZ, Fjeld MG, Smith HJ, Flato B, Ogaard B, Larheim TA: Craniofacial growth disturbance is related to temporomandibular joint abnormality in patients with juvenile idiopathic arthritis, but normal facial profile was also found at the 27-year

EP

follow-up. Scand J Rheumatol:39(5):373-9,2010. Arvidsson LZ, Flato B, Larheim TA: Radiographic TMJ abnormalities in patients with

AC C

juvenile idiopathic arthritis followed for 27 years. Oral Surg Oral Med Oral Pathol Oral Radiol Endod:108(1):114-23,2009. Arvidsson LZ, Smith HJ, Flato B, Larheim TA: Temporomandibular joint findings in adults with long-standing juvenile idiopathic arthritis: CT and MR imaging assessment. Radiology:256(1):191-200,2010.

ACCEPTED MANUSCRIPT 25

Assaf AT, Kahl-Nieke B, Feddersen J, Habermann CR: Is high-resolution ultrasonography suitable for the detection of temporomandibular joint involvement in

RI PT

children with juvenile idiopathic arthritis? Dentomaxillofac Radiol:42(3):20110379,2013. Avenarius DM, Ording Muller LS, Eldevik P, Owens CM, Rosendahl K: The paediatric wrist revisited-findings of bony depressions in healthy children on radiographs compared

SC

to MRI. Pediatr Radiol:42(7):791-8,2012.

Avrahami E, Segal R, Solomon A, Garti A, Horowitz I, Caspi D et al.: Direct coronal

M AN U

high resolution computed tomography of the temporomandibular joints in patients with rheumatoid arthritis. J Rheumatol:16(3):298-301,1989.

Bakke M, Zak M, Jensen BL, Pedersen FK, Kreiborg S: Orofacial pain, jaw function, and temporomandibular disorders in women with a history of juvenile chronic arthritis or

TE D

persistent juvenile chronic arthritis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod:92(4):406-14,2001.

EP

Barghan S, Tetradis S, Mallya S: Application of cone beam computed tomography for assessment of the temporomandibular joints. Aust Dent J:57 Suppl 1:109-18,2012.

AC C

Barr T, Carmichael NM, Sandor GK: Juvenile idiopathic arthritis: a chronic pediatric musculoskeletal condition with significant orofacial manifestations. J Can Dent Assoc:74(9):813-21,2008. Berntson L, Andersson GB, Fasth A, Herlin T, Kristinsson J, Lahdenne P et al.: Incidence of juvenile idiopathic arthritis in the Nordic countries. A population based study with special reference to the validity of the ILAR and EULAR criteria. J

ACCEPTED MANUSCRIPT 26

Rheumatol:30(10):2275-82,2003. Billiau AD, Hu Y, Verdonck A, Carels C, Wouters C: Temporomandibular joint arthritis

dentofacial morphology. J Rheumatol:34(9):1925-33,2007.

RI PT

in juvenile idiopathic arthritis: prevalence, clinical and radiological signs, and relation to

Breton S, Jousse-Joulin S, Finel E, Marhadour T, Colin D, de PL et al.: Imaging

M AN U

Semin Arthritis Rheum:41(5):698-711,2012.

SC

approaches for evaluating peripheral joint abnormalities in juvenile idiopathic arthritis.

Brooks SL, Brand JW, Gibbs SJ, Hollender L, Lurie AG, Omnell KA et al.: Imaging of the temporomandibular joint: a position paper of the American Academy of Oral and Maxillofacial Radiology. Oral Surg Oral Med Oral Pathol Oral Radiol Endod:83(5):609-

TE D

18,1997.

Calabro JJ: Rheumatoid arthritis: diagnosis and management. Clin Symp:38(2):132,1986.

EP

Calabro JJ, Holgerson WB, Sonpal GM, Khoury MI. Juvenile rheumatoid arthritis: a general review and report of 100 patients observed for 15 years. SeminArthritis Rheum.

AC C

1976;5(3):257-98.

Cannizzaro E, Schroeder S, Muller LM, Kellenberger CJ, Saurenmann RK: Temporomandibular joint involvement in children with juvenile idiopathic arthritis. J Rheumatol:38(3):510-5,2011. Carlsson GE, Oberg T: Remodelling of the temporomandibular joints. Oral Sci

ACCEPTED MANUSCRIPT 27

Rev:6(0):53-86,1974. Cascone P, Rinaldi F, Pagnoni M, Marianetti TM, Tedaldi M: Three-dimensional

RI PT

temporomandibular joint modeling and animation. J Craniofac Surg:19(6):1526-31,2008. Cevidanes LH, Bailey LJ, Tucker GR, Jr., Styner MA, Mol A, Phillips CL et al.: Superimposition of 3D cone-beam CT models of orthognathic surgery patients.

SC

Dentomaxillofac Radiol:34(6):369-75,2005.

M AN U

Cevidanes LH, Hajati AK, Paniagua B, Lim PF, Walker DG, Palconet G et al.: Quantification of condylar resorption in temporomandibular joint osteoarthritis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod:110(1):110-7,2010. Cha JY, Mah J, Sinclair P: Incidental findings in the maxillofacial area with 3-

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dimensional cone-beam imaging. Am J Orthod Dentofacial Orthop:132(1):7-14,2007. Chavhan GB, Babyn PS, Jankharia BG, Cheng HL, Shroff MM: Steady-state MR imaging sequences: physics, classification, and clinical applications.

EP

Radiographics:28(4):1147-60,2008.

AC C

Dahlstrom L, Lindvall AM: Assessment of temporomandibular joint disease by panoramic radiography: reliability and validity in relation to tomography. Dentomaxillofac Radiol:25(4):197-201,1996. Elias FM, Birman EG, Matsuda CK, Oliveira IR, Jorge WA: Ultrasonographic findings in normal temporomandibular joints. Braz Oral Res:20(1):25-32,2006. Emshoff R, Brandlmaier I, Bodner G, Rudisch A: Condylar erosion and disc

ACCEPTED MANUSCRIPT 28

displacement: detection with high-resolution ultrasonography. J Oral Maxillofac Surg:61(8):877-81,2003.

RI PT

Emshoff R, Jank S, Rudisch A, Bodner G: Are high-resolution ultrasonographic signs of disc displacement valid? J Oral Maxillofac Surg:60(6):623-8,2002.

Engstrom AL, Wanman A, Johansson A, Keshishian P, Forsberg M: Juvenile arthritis and

M AN U

study. J Orofac Pain:21(2):120-6,2007.

SC

development of symptoms of temporomandibular disorders: a 15-year prospective cohort

European Commission: Radiation protection no. 172: Evidence based guidelines on cone beam CT for dental and maxillofacial radiology. European Commission Guidelines:2012. Farina D, Bodin C, Gandolfi S, De GW, Borghesi A, Maroldi R: TMJ disorders and pain:

TE D

assessment by contrast-enhanced MRI. Eur J Radiol:70(1):25-30,2009. Farronato G, Garagiola U, Carletti V, Cressoni P, Mercatali L, Farronato D: Change in condylar and mandibular morphology in juvenile idiopathic arthritis: Cone Beam

EP

volumetric imaging. Minerva Stomatol:59(10):519-34,2010.

AC C

Fjeld M, Arvidsson L, Smith HJ, Flato B, Ogaard B, Larheim T: Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood. Pediatr Rheumatol Online J:8:13,2010. Gabriel SE, Michaud K: Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis Res Ther:11(3):229,2009.

ACCEPTED MANUSCRIPT 29

Gewanter HL, Roghmann KJ, Baum J: The prevalence of juvenile arthritis. Arthritis Rheum:26(5):599-603,1983.

RI PT

Greess H, Anders K: [Indications for validity of computed tomography and magnetic resonance imaging of the temporomandibular joint]. Rontgenpraxis:56(1):1-11,2005.

Hatcher DC: Operational principles for cone-beam computed tomography. J Am Dent

SC

Assoc:141 Suppl 3:3S-6S,2010.

M AN U

Hinton RJ: Genes that regulate morphogenesis and growth of the temporomandibular joint: a review. Dev Dyn:243(7):864-74,2014.

Hintze H, Wiese M, Wenzel A: Cone beam CT and conventional tomography for the detection of morphological temporomandibular joint changes. Dentomaxillofac

TE D

Radiol:36(4):192-7,2007.

Honda K, Larheim TA, Maruhashi K, Matsumoto K, Iwai K: Osseous abnormalities of the mandibular condyle: diagnostic reliability of cone beam computed tomography

EP

compared with helical computed tomography based on an autopsy material.

AC C

Dentomaxillofac Radiol:35(3):152-7,2006. Honey OB, Scarfe WC, Hilgers MJ, Klueber K, Silveira AM, Haskell BS et al.: Accuracy of cone-beam computed tomography imaging of the temporomandibular joint: comparisons with panoramic radiology and linear tomography. Am J Orthod Dentofacial Orthop:132(4):429-38,2007. Hu YS, Schneiderman ED, Harper RP: The temporomandibular joint in juvenile

ACCEPTED MANUSCRIPT 30

rheumatoid arthritis: Part II. Relationship between computed tomographic and clinical findings. Pediatr Dent:18(4):312-9,1996.

RI PT

Huntjens E, Kiss G, Wouters C, Carels C: Condylar asymmetry in children with juvenile idiopathic arthritis assessed by cone-beam computed tomography. Eur J Orthod:30(6):545-51,2008.

SC

Ince DO, Ince A, Moore TL: Effect of methotrexate on the temporomandibular joint and

Orthop:118(1):75-83,2000.

M AN U

facial morphology in juvenile rheumatoid arthritis patients. Am J Orthod Dentofacial

Jank S, Emshoff R, Norer B, Missmann M, Nicasi A, Strobl H et al.: Diagnostic quality of dynamic high-resolution ultrasonography of the TMJ--a pilot study. Int J Oral

TE D

Maxillofac Surg:34(2):132-7,2005.

Jank S, Haase S, Strobl H, Michels H, Hafner R, Missmann M et al.: Sonographic investigation of the temporomandibular joint in patients with juvenile idiopathic arthritis:

EP

a pilot study. Arthritis Rheum:57(2):213-8,2007.

AC C

Johnson K: Imaging of juvenile idiopathic arthritis. Pediatr Radiol:36(8):743-58,2006. Kaipiainen-Seppanen O, Savolainen A: Changes in the incidence of juvenile rheumatoid arthritis in Finland. Rheumatology (Oxford):40(8):928-32,2001. Karhulahti T, Ronning O, Jamsa T: Mandibular condyle lesions, jaw movements, and occlusal status in 15-year-old children with juvenile rheumatoid arthritis. Scand J Dent Res:98(1):17-26,1990.

ACCEPTED MANUSCRIPT 31

Karlo CA, Patcas R, Kau T, Watzal H, Signorelli L, Muller L et al.: MRI of the temporomandibular joint: which sequence is best suited to assess the cortical bone of the mandibular condyle? A cadaveric study using micro-CT as the standard of reference. Eur

RI PT

Radiol:22(7):1579-85,2012.

Karlo CA, Stolzmann P, Habernig S, Muller L, Saurenmann T, Kellenberger CJ: Size,

SC

shape and age-related changes of the mandibular condyle during childhood. Eur Radiol:20(10):2512-7,2010.

M AN U

Karmazyn B, Lin C, Persohn SA, Buckwalter KA: Feasibility of mapping T2 relaxation time in the pediatric metacarpal head with a 3-T MRI system. AJR Am J Roentgenol:198(6):W602-W604,2012.

Koos B, Gassling V, Bott S, Tzaribachev N, Godt A: Pathological changes in the TMJ

TE D

and the length of the ramus in patients with confirmed juvenile idiopathic arthritis. J Craniomaxillofac Surg:42(8):1802-7,2014.

EP

Koos B, Twilt M, Kyank U, Fischer-Brandies H, Gassling V, Tzaribachev N: Reliability of clinical symptoms in diagnosing temporomandibular joint arthritis in juvenile

AC C

idiopathic arthritis. J Rheumatol:41(9):1871-7,2014. Koos B, Tzaribachev N, Bott S, Ciesielski R, Godt A: Classification of temporomandibular joint erosion, arthritis, and inflammation in patients with juvenile idiopathic arthritis. J Orofac Orthop:74(6):506-19,2013. Kreiborg S, Bakke M, Kirkeby S, Michler L, Vedtofte P, Seidler B et al.: Facial growth and oral function in a case of juvenile rheumatoid arthritis during an 8-year period. Eur J

ACCEPTED MANUSCRIPT 32

Orthod:12(2):119-34,1990. Krishnamoorthy B, Mamatha N, Kumar VA: TMJ imaging by CBCT: Current scenario.

RI PT

Ann Maxillofac Surg:3(1):80-3,2013. Kuseler A, Pedersen TK, Gelineck J, Herlin T: A 2 year followup study of enhanced

magnetic resonance imaging and clinical examination of the temporomandibular joint in

SC

children with juvenile idiopathic arthritis. J Rheumatol:32(1):162-9,2005.

M AN U

Kuseler A, Pedersen TK, Herlin T, Gelineck J: Contrast enhanced magnetic resonance imaging as a method to diagnose early inflammatory changes in the temporomandibular joint in children with juvenile chronic arthritis. J Rheumatol:25(7):1406-12,1998. Landes CA, Goral W, Mack MG, Sader R: 3-D sonography for diagnosis of

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osteoarthrosis and disk degeneration of the temporomandibular joint, compared with MRI. Ultrasound Med Biol:32(5):627-32,2006. Lanni S, Wood M, Ravelli A, Magni MS, Emery P, Wakefield RJ: Towards a role of

EP

ultrasound in children with juvenile idiopathic arthritis. Rheumatology

AC C

(Oxford):52(3):413-20,2013.

Larheim TA, Abrahamsson AK, Kristensen M, Arvidsson LZ: Temporomandibular joint diagnostics using CBCT. Dentomaxillofac Radiol:44(1):20140235,2015. Larheim TA, Kolbenstvedt A: High-resolution computed tomography of the osseous temporomandibular joint. Some normal and abnormal appearances. Acta Radiol Diagn (Stockh):25(6):465-9,1984.

ACCEPTED MANUSCRIPT 33

Melchiorre D, Calderazzi A, Maddali BS, Cristofani R, Bazzichi L, Eligi C et al.: A comparison of ultrasonography and magnetic resonance imaging in the evaluation of temporomandibular joint involvement in rheumatoid arthritis and psoriatic arthritis.

RI PT

Rheumatology (Oxford):42(5):673-6,2003.

Melchiorre D, Falcini F, Kaloudi O, Bandinelli F, Nacci F, Matucci CM: Sonographic

SC

evaluation of the temporomandibular joints in juvenile idiopathic arthritis(). J Ultrasound:13(1):34-7,2010.

M AN U

Melis M, Secci S, Ceneviz C: Use of ultrasonography for the diagnosis of temporomandibular joint disorders: a review. Am J Dent:20(2):73-8,2007. Meng F, Liu Y, Hu K, Zhao Y, Kong L, Zhou S: A comparative study of the skeletal

Med:54(3):191-4,2008.

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morphology of the temporo-mandibular joint of children and adults. J Postgrad

Meyers AB, Laor T: Magnetic resonance imaging of the temporomandibular joint in

EP

children with juvenile idiopathic arthritis. Pediatr Radiol:43(12):1632-41,2013. Miracle AC, Mukherji SK: Conebeam CT of the head and neck, part 1: physical

AC C

principles. AJNR Am J Neuroradiol:30(6):1088-95,2009. Mouterde G, Carotti M, D'Agostino MA: [Contrast-enhanced ultrasound in musculoskeletal diseases]. J Radiol:90(1 Pt 2):148-55,2009. Muller L, Kellenberger CJ, Cannizzaro E, Ettlin D, Schraner T, Bolt IB et al.: Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot

ACCEPTED MANUSCRIPT 34

study comparing clinical examination and ultrasound to magnetic resonance imaging. Rheumatology (Oxford):48(6):680-5,2009.

RI PT

Muller LS, Avenarius D, Damasio B, Eldevik OP, Malattia C, Lambot-Juhan K et al.: The paediatric wrist revisited: redefining MR findings in healthy children. Ann Rheum Dis:70(4):605-10,2011.

SC

Noar JH, Pabari S: Cone beam computed tomography--current understanding and

M AN U

evidence for its orthodontic applications? J Orthod:40(1):5-13,2013.

Nozawa-Inoue K, Amizuka N, Ikeda N, Suzuki A, Kawano Y, Maeda T: Synovial membrane in the temporomandibular joint--its morphology, function and development. Arch Histol Cytol:66(4):289-306,2003.

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Oberg T, Carlsson GE, Fajers CM: The temporomandibular joint. A morphologic study on a human autopsy material. Acta Odontol Scand:29(3):349-84,1971. Orth RC, Wallace MJ, Kuo MD: C-arm cone-beam CT: general principles and technical

AC C

20,2008.

EP

considerations for use in interventional radiology. J Vasc Interv Radiol:19(6):814-

Ostergaard M, Klarlund M: Importance of timing of post-contrast MRI in rheumatoid arthritis: what happens during the first 60 minutes after IV gadolinium-DTPA? Ann Rheum Dis:60(11):1050-4,2001. Ostergaard M, Peterfy C, Conaghan P, McQueen F, Bird P, Ejbjerg B et al.: OMERACT Rheumatoid Arthritis Magnetic Resonance Imaging Studies. Core set of MRI

ACCEPTED MANUSCRIPT 35

acquisitions, joint pathology definitions, and the OMERACT RA-MRI scoring system. J Rheumatol:30(6):1385-6,2003.

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Parra DA, Chan M, Krishnamurthy G, Spiegel L, Amaral JG, Temple MJ et al.: Use and accuracy of US guidance for image-guided injections of the temporomandibular joints in children with arthritis. Pediatr Radiol:40(9):1498-504,2010.

SC

Patel A, Tee BC, Fields H, Jones E, Chaudhry J, Sun Z: Evaluation of cone-beam computed tomography in the diagnosis of simulated small osseous defects in the

M AN U

mandibular condyle. Am J Orthod Dentofacial Orthop:145(2):143-56,2014. Pearson MH, Ronning O: Lesions of the mandibular condyle in juvenile chronic arthritis. Br J Orthod:23(1):49-56,1996.

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Pedersen TK: Clinical aspects of orthodontic treatment for children with juvenile chronic arthritis. Acta Odontol Scand:56(6):366-8,1998. Pedersen TK, Jensen JJ, Melsen B, Herlin T: Resorption of the temporomandibular

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condylar bone according to subtypes of juvenile chronic arthritis. J

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Rheumatol:28(9):2109-15,2001.

Pedersen TK, Kuseler A, Gelineck J, Herlin T: 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. J Rheumatol:35(8):1668-75,2008. Petersson A: What you can and cannot see in TMJ imaging--an overview related to the

ACCEPTED MANUSCRIPT 36

RDC/TMD diagnostic system. J Oral Rehabil:37(10):771-8,2010. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J et al.:

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International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol:31(2):390-2,2004. Ravelli A, Martini A: Juvenile idiopathic arthritis. Lancet:369(9563):767-78,2007.

SC

Ravelli A, Varnier GC, Oliveira S, Castell E, Arguedas O, Magnani A et al.: Antinuclear

M AN U

antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis. Arthritis Rheum:63(1):267-75,2011. Reichert IL, Benjamin M, Gatehouse PD, Chappell KE, Holmes J, He T et al.: Magnetic resonance imaging of periosteum with ultrashort TE pulse sequences. J Magn Reson

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Imaging:19(1):99-107,2004.

Ribeiro RF, Tallents RH, Katzberg RW, Murphy WC, Moss ME, Magalhaes AC et al.: The prevalence of disc displacement in symptomatic and asymptomatic volunteers aged 6

EP

to 25 years. J Orofac Pain:11(1):37-47,1997.

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Ringold S, Cron RQ: The temporomandibular joint in juvenile idiopathic arthritis: frequently used and frequently arthritic. Pediatr Rheumatol Online J:7:11,2009. Ringold S, Thapa M, Shaw EA, Wallace CA: Heterotopic ossification of the temporomandibular joint in juvenile idiopathic arthritis. J Rheumatol:38(7):1423-8,2011. Ronchezel MV, Hilario MO, Goldenberg J, Lederman HM, Faltin K, Jr., de Azevedo MF et al.: Temporomandibular joint and mandibular growth alterations in patients with

ACCEPTED MANUSCRIPT 37

juvenile rheumatoid arthritis. J Rheumatol:22(10):1956-61,1995. Ronning O, Valiaho ML, Laaksonen AL: The involvement of the temporomandibular

RI PT

joint in juvenile rheumatoid arthritis. Scand J Rheumatol:3(2):89-96,1974. Sanal HT, Bae WC, Pauli C, Du J, Statum S, Znamirowski R et al.: Magnetic resonance imaging of the temporomandibular joint disc: feasibility of novel quantitative magnetic

SC

resonance evaluation using histologic and biomechanical reference standards. J Orofac

M AN U

Pain:25(4):345-53,2011.

Scarfe WC, Farman AG, Sukovic P: Clinical applications of cone-beam computed tomography in dental practice. J Can Dent Assoc:72(1):75-80,2006. Schneider R, Passo MH: Juvenile rheumatoid arthritis. Rheum Dis Clin North

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Am:28(3):503-30,2002.

Scolozzi P, Bosson G, Jaques B: Severe isolated temporomandibular joint involvement in

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juvenile idiopathic arthritis. J Oral Maxillofac Surg:63(9):1368-71,2005. Sheybani EF, Khanna G, White AJ, Demertzis JL: Imaging of juvenile idiopathic

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arthritis: a multimodality approach. Radiographics:33(5):1253-73,2013. Sidiropoulou-Chatzigianni S, Papadopoulos MA, Kolokithas G: Dentoskeletal morphology in children with juvenile idiopathic arthritis compared with healthy children. J Orthod:28(1):53-8,2001. Silva MA, Wolf U, Heinicke F, Bumann A, Visser H, Hirsch E: Cone-beam computed tomography for routine orthodontic treatment planning: a radiation dose evaluation. Am J

ACCEPTED MANUSCRIPT 38

Orthod Dentofacial Orthop:133(5):640-5,2008. Smartt JM, Jr., Low DW, Bartlett SP: The pediatric mandible: I. A primer on growth and

RI PT

development. Plast Reconstr Surg:116(1):14e-23e,2005. Sperber GH: First year of life: prenatal craniofacial development. Cleft Palate Craniofac J:29(2):109-11,1992.

SC

Stabrun AE, Larheim TA, Rosler M, Haanaes HR: Impaired mandibular function and its

Orthod:9(1):43-50,1987.

M AN U

possible effect on mandibular growth in juvenile rheumatoid arthritis. Eur J

Stehling C, Vieth V, Bachmann R, Nassenstein I, Kugel H, Kooijman H et al.: Highresolution magnetic resonance imaging of the temporomandibular joint: image quality at

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1.5 and 3.0 Tesla in volunteers. Invest Radiol:42(6):428-34,2007. Stoll ML, Morlandt AB, Teerawattanapong S, Young D, Waite PD, Cron RQ: Safety and efficacy of intra-articular infliximab therapy for treatment-resistant temporomandibular

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9,2013.

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joint arthritis in children: a retrospective study. Rheumatology (Oxford):52(3):554-

Stoll ML, Sharpe T, Beukelman T, Good J, Young D, Cron RQ: Risk factors for temporomandibular joint arthritis in children with juvenile idiopathic arthritis. J Rheumatol:39(9):1880-7,2012. Stoustrup P, Kristensen KD, Verna C, Kuseler A, Pedersen TK, Herlin T: Intra-articular steroid injection for temporomandibular joint arthritis in juvenile idiopathic arthritis: A

ACCEPTED MANUSCRIPT 39

systematic review on efficacy and safety. Semin Arthritis Rheum:43(1):63-70,2013. Stratemann SA, Huang JC, Maki K, Hatcher DC, Miller AJ: Evaluating the mandible

RI PT

with cone-beam computed tomography. Am J Orthod Dentofacial Orthop:137(4 Suppl):S58-S70,2010.

Stratemann SA, Huang JC, Maki K, Miller AJ, Hatcher DC: Comparison of cone beam

SC

computed tomography imaging with physical measures. Dentomaxillofac

M AN U

Radiol:37(2):80-93,2008.

Suomalainen A, Pakbaznejad EE, Robinson S: Dentomaxillofacial imaging with panoramic views and cone beam CT. Insights Imaging:6(1):1-16,2015. Svensson B, Adell R, Kopp S: Temporomandibular disorders in juvenile chronic arthritis

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patients. A clinical study. Swed Dent J:24(3):83-92,2000.

Symmons DP, Jones M, Osborne J, Sills J, Southwood TR, Woo P: Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology

EP

Group National Diagnostic Register. J Rheumatol:23(11):1975-80,1996.

AC C

Thompson JR, Christiansen E, Hasso AN, Hinshaw DB, Jr.: Temporomandibular joints: high-resolution computed tomographic evaluation. Radiology:150(1):105-10,1984. Tok F, Demirkaya E, Ozcakar L: Musculoskeletal ultrasound in pediatric rheumatology. Pediatr Rheumatol Online J:9:25,2011. Twilt M, Mobers SM, Arends LR, Ten CR, van Suijlekom-Smit L: Temporomandibular involvement in juvenile idiopathic arthritis. J Rheumatol:31(7):1418-22,2004.

ACCEPTED MANUSCRIPT 40

Twilt M, Schulten AJ, Nicolaas P, Dulger A, van Suijlekom-Smit LW: Facioskeletal changes in children with juvenile idiopathic arthritis. Ann Rheum Dis:65(6):823-5,2006.

RI PT

Twilt M, Schulten AJ, Prahl-Andersen B, van Suijlekom-Smit LW: Long-term follow-up of craniofacial alterations in juvenile idiopathic arthritis. Angle Orthod:79(6):105762,2009.

SC

Tzaribachev N, Fritz J, Horger M: Spectrum of magnetic resonance imaging appearances

Radiol:50(10):1182-6,2009.

M AN U

of juvenile temporomandibular joints (TMJ) in non-rheumatic children. Acta

Ueda M, Yonetsu K, Ohki M, Yamada T, Kitamori H, Nakamura T: Curvature analysis of the mandibular condyle. Dentomaxillofac Radiol:32(2):87-92,2003.

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Vaid YN, Dunnavant FD, Royal SA, Beukelman T, Stoll ML, Cron RQ: Imaging of the temporomandibular joint in juvenile idiopathic arthritis. Arthritis Care Res (Hoboken ):66(1):47-54,2014.

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Vilanova JC, Barcelo J, Puig J, Remollo S, Nicolau C, Bru C: Diagnostic imaging: magnetic resonance imaging, computed tomography, and ultrasound. Semin Ultrasound

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CT MR:28(3):184-91,2007. von Kalle T, Winkler P, Stuber T: Contrast-enhanced MRI of normal temporomandibular joints in children--is there enhancement or not? Rheumatology (Oxford):52(2):3637,2013. von KT, Stuber T, Winkler P, Maier J, Hospach T: Early detection of temporomandibular

ACCEPTED MANUSCRIPT 41

joint arthritis in children with juvenile idiopathic arthritis - the role of contrast-enhanced MRI. Pediatr Radiol:2014.

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Weiss PF, Arabshahi B, Johnson A, Bilaniuk LT, Zarnow D, Cahill AM et al.: 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.

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Arthritis Rheum:58(4):1189-96,2008.

Yura S, Nobata K, Shima T: Hyperintensity signal in the joint space of the

M AN U

temporomandibular joint on fat-saturated T2-weighted magnetic resonance imaging. Br J Oral Maxillofac Surg:48(8):621-3,2010.

Zain-Alabdeen EH, Alsadhan RI: A comparative study of accuracy of detection of surface osseous changes in the temporomandibular joint using multidetector CT and cone

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beam CT. Dentomaxillofac Radiol:41(3):185-91,2012. Zulian F, Martini G, Gobber D, Plebani M, Zacchello F, Manners P: Triamcinolone

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acetonide and hexacetonide intra-articular treatment of symmetrical joints in juvenile

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idiopathic arthritis: a double-blind trial. Rheumatology (Oxford):43(10):1288-91,2004.

ACCEPTED MANUSCRIPT Legends to figures Figure 1 The temporomandibular joint is the articulation between the temporal bone (f=mandibular fossa) and the mandibular condyle (c=condyle), with an articular disc located between these bones (d=disc). The disc separates the joint into an upper cavity and a lower cavity which are not communicating. The joint is covered by a capsule. The synovial membrane lines the inner surface of

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the fibrous capsule of the temporomandibular joint and the margins of the articular disc (it does not cover the articular surface of the joint and articular disc (except for the bilaminar zone)). (ca=capsule). e=articular eminence.

Figure 2 Lateral cephalogram in a 16 year old girl. Normal findings.

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Figure 3 Panoramic radiograph(PTG) of a 13 year old girl with JIA showing destructive changes and flattening on both condyles right and left.

destructed and flattened condyle.

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Figure 4a Detailed Cone Beam CT image of the left TMJ in a young girl with JIA, showing a

Figure 4b 3D reconstructed CBCT showing craniofacial asymmetry in a 10-year-old girl with JIA. The mandible deviates to the right(black lines), the right mandibular ramus is shortened, and the right maxilla is tilted cranially.

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Figure 4c Isolated representation of the asymmetric developmentof the mandible. Dorsal-lateral left, dorsal and dorsal-lateral right CBCT views allows for comparison of left and right sides. The condylar head and the ramus are hypoplastic.

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Figure 5 High resolution, coronal ultrasound images of a) a normal, right TMJ (open mouth) showing

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a normal lateral capsule (double arrow) and b) a left-sided condylar irregularity (arrow) in a 13 year old female with JIA (closed mouth). c=mandibular condyle, r= mandibular ramus, ae=articular condyle. The full role of ultrasound in the detection of acute inflammation and permanent change is still not clarified.

Figure 6 Sagittal/oblique, proton weighted MR image (3T) in a 14-year old girl, depicting the anatomy of a normal TMJ. The temporomandibular articulation consists of the mandibular condyle (c) caudally and the articular fossa of the temporal bone cranially which is bounded by the articular eminence (ae) anteriorly. The articular disc (long arrow) divides the joint into an upper cavity (short arrow) and a lower cavity (stippled arrow), which do not communicate unless there is a discal derangement. me= meatus extrernus, lpm=lateral pterygoid muscle.

Figure 7 Coronal 3D T1-weighted MR-image (flash, dynamic, temporal resolution 4 sec.) subtraction image (3T) in a 12 year old girl, showing symmetrical enhancement of both TMJs (arrows). c=mandibular condyle. The role of contrast-enhanced MR images in TMJ arthritis is still under investigation, however, several studies suggest that contrast-enhanced images are helpful.

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Figure 8 Sagittal/oblique, T2-weighted MR image (3T) in a 14 year old girl with JIA, showing a mild joint effusion (arrow). The effusion is located primarily in the inferior cavity. Interestingly the condyle (=c) is flattened (compare changes with normal anatomy in Figure 5), indicating permanent change.

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Figure 9 Sagittal/oblique fat-suppressed (WE), a) pre- and b) post-contrast T1-weighted MR images

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(3T) in a girl (same as in figure 8), showing vivid synovial enhancement, indicative of synovitis. There is also subtle enhancement of bone marrow in the adjacent mandibular condyle. These changes are considered typically early features of active arthritis of TMJs.

ACCEPTED MANUSCRIPT Table 1. Classification of JIA into seven subtypes according to the ILAR criteria (Petty et al., 2004; Ravelli et al., 2011) .

Systemic arthritis: arthritis in 1 or more joints with/or proceeded by, at least 2 weeks of fever. Documentation of daily signs or symptoms for at least 3 days is required, accompanied with at least one of the following: evanescent rash, generalized lymphoadenopathy, hepato-splenomegaly, serositis.

2.

Oligoarthritis: up to 4 joints affected in the first 6 months

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a)* Extended: if more than 4 joints are affected after the 6 months period b) * Persistent: if up to 4 joints remain affected after the 6 months period

RF positive Polyarthritis: more than four joints affected in the first 6 months and positive RF (rheumatoid factor) on at least 2 investigations 3 months apart

4.

*RF negative Polyarthritis: more than four joints affected in the first 6 months and negative RF testing.

5.

*Psoriatic arthritis: arthritis and psoriasis, or arthritis and 2 or more of the following: nail pitting,

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onycholysis , dactylitis, , and/or family history of psoriasis (in a first-degree relative). 6.

ERA (enthesitis related arthritis): arthritis and/or enthesitis with 2 or more of the following: presence or history of sacroiliac joint tenderness with/without local inflammatory pain; positive HLA B27 antigen;

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arthritis onset in a male (aged 6 years or older ); symptomatic acute anterior uveitis; history of ankylosing spondylitis, enthesitis-related arthritis, sacroiliitis with inflammatory bowel disease, Reiter's syndrome, or acute anterior uveitis in a first-degree relative. 7.

*Undifferentiated arthritis: arthritis that either fulfils criteria for 2 or more or does not fulfill criteria for any

•

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of the above categories .

Table modified from source reference (Petty et al., 2004) *: When ANA+, patients in both subtypes of oligoarthritis along with other subtypes (marked*) are suggested to share the same characteristics and thus represent a homogeneous subgroup. (Ravelli et al., 2011).

Table 2. Box: search strategy and selection criteria: MeSH terms PubMed was searched for articles published on Juvenile Idiopathic Arthritis over the last 50 years (1962- 2013) with following matching MeSH term strings:

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((( "Arthritis, Juvenile Rheumatoid/anatomy and histology"[Majr] OR "Arthritis, Juvenile Rheumatoid/complications"[Majr] OR "Arthritis, Juvenile Rheumatoid/diagnosis"[Majr] OR "Arthritis, Juvenile Rheumatoid/radiography"[Majr] OR "Arthritis, Juvenile Rheumatoid/radionuclide imaging"[Majr] OR "Arthritis, Juvenile Rheumatoid/ultrasonography"[Majr] ))) AND (((("Magnetic Resonance Imaging"[Majr]) OR "Tomography, X-Ray Computed"[Majr]) OR "Radiography"[Majr]) OR "Ultrasonography"[Majr]).We also searched using the MeSH terms: ((((( "Arthritis, Juvenile Rheumatoid/anatomy and histology"[Majr] OR "Arthritis, Juvenile Rheumatoid/complications"[Majr] OR "Arthritis, Juvenile Rheumatoid/diagnosis"[Majr] OR "Arthritis, Juvenile Rheumatoid/radiography"[Majr] OR "Arthritis, Juvenile Rheumatoid/radionuclide imaging"[Majr] OR "Arthritis, Juvenile Rheumatoid/ultrasonography"[Majr] ))) AND (((("Magnetic Resonance Imaging"[Majr]) OR "Tomography, X-Ray Computed"[Majr]) OR "Radiography"[Majr]) OR "Ultrasonography"[Majr]))). Again, we searched using the terms:("Arthritis, Juvenile Rheumatoid"[Mesh]) AND ((((((("Magnetic Resonance Imaging"[Mesh]) OR "Cone-Beam Computed Tomography"[Mesh]) OR "Radiography"[Mesh]) OR "Ultrasonography"[Mesh]) OR "Radiography, Panoramic"[Mesh])) AND temporomandibular joint). Moreover, we continued our search using these terms: ("Anatomy"[Majr]) AND "Temporomandibular Joint"[Majr]. And finally we used these terms: ((("Diagnostic Imaging"[Mesh]) AND "Temporomandibular Joint"[Mesh])) AND "Child"[Mesh].

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Imaging method

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Table 3. Effective radiation dose from cephalometric and panoramic radiograph (PTG), cone beam computed tomography (CBCT) and multislice computed tomography (MSCT) given in µSv and in mSv. For CBCT, ranges and median values (in parentheses) are provided according to guidelines issued by the European Commission in 2012 (6). (FOV=field of view). Effective dose (µSv) Effective dose (mSv)

Cephalometric radiograph 10 cm)* 30-1073 (87) 0.03-1.07 (0.09) Dentoalveolar CBCT (FOV height