First described by Thomas Phaire in the first English-language textbook of pediatrics as a group of conditions characterized by “stifnes or starcknenes of limes” (1545), mentioned by Cornil in 1864 and further detailed in publications by Mayer Saül Diamantberger (1891) and George Frederic Still (1897) [1–3], juvenile idiopathic arthritis (JIA) encompasses a heterogeneous set of chronic inflammatory diseases in children, essentially identified by chronic inflammatory arthritis with onset before the age of 16 years and of unknown origin. Current naming and classification, though under criticism in the recent decades, are due to the definitions revised in 1997 and 2001 by the International League of Associations for Rheumatology (ILAR), which agreed to merge the terms “juvenile rheumatoid arthritis” and “juvenile chronic arthritis”, respectively adopted by the North-American and the European researchers. ILAR classification criteria define seven JIA subtypes, depending on the association with systemic features, the number of joints affected in the first six months of the disease and its course, the presence/absence of IgM rheumatoid factor (RF) on at least two occasions at least 3 months apart, the occurrence of psoriasis or psoriatic features, and the axial and entheseal involvement, namely: the systemic, the oligoarticular (persistent or extended, based on the number of joints cumulatively involved after the first 6 months of disease), the polyarticular RF-negative, the polyarticular RF-positive, the psoriatic, the enthesitis-related arthritis (ERA), and the undifferentiated arthritis subtype [4–8]. The estimated incidence of JIA is 1.3–22.6 per 100,000, higher among people of White European ancestry than among those of Asian ancestry [9]. JIA typically presents with joint inflammation, swelling, morning stiffness, pain, and limited mobility involving one or more joints [10]. Though the distribution of joints involved may vary across the different JIA subtypes, the most frequently affected joint is the knee, followed by the ankle, the wrist, the second and third proximal interphalangeal joints, the second and third metacarpophalangeal joints, the elbow, the cervical spine, and the hip. The sternoclavicular, acromioclavicular, distal interphalangeal, and foot interphalangeal joints are rarely affected in children with JIA [9–11].

Arthritis of the temporomandibular joint (TMJ) does not typically manifest with joint swelling or pain. Physical exam findings of TMJs can be detectable late in the disease process when the bone growth has been altered by the arthritis. This makes it difficult to capture TMJ involvement at the early stages, which conversely would be of much benefit for avoiding irreversible damage and impaired functions. Further, TMJ has great remodeling capabilities during developmental ages, which reinforces the urgency of harnessing the full potential rescue of compromised joints [12, 13].

For many years, TMJ has been regarded as the forgotten joint by pediatric rheumatologists, whereas its involvement in JIA attracted a lot of interest among dentists, with a substantial niche focus on the repercussions on mandibular growth and the subsequent abnormal secondary occlusion. Nonetheless, in the past two decades, there has been growing evidence of high frequent involvement of TMJ in JIA patients. Depending on the diagnostic method used (clinical and/or imaging-based), the examiner specialty (pediatrician, rheumatologist, orthodontist, maxillo-facial surgeon), the JIA subtype and population investigated, studies have reported from forty to ninety-six percent of JIA patients with TMJ arthritis along the disease course [14–16].

Early recognition for timely and appropriate treatment is the key to effective multidisciplinary management of TMJ in JIA and the reduction of irreversible damage and subjective discomfort. In the present perspective, diagnostic clinical and imaging tools currently available for early detection of TMJ involvement in JIA will be presented and discussed.

The complex formed by the TMJs and the masticatory muscles allows the mandible to move up and down, side to side, and forward and back. The proper alignment of the mandible and the TMJs is also pivotal for several smooth actions that we unconsciously perform many times a day, including chewing, talking, yawning, and swallowing.

The peculiar structure of TMJ distinguishes it from the other joints, since it consists of a bilateral synovial diarthrosis, defined as “ginglymoarthrodial joint”, with fibrous cartilage covering the articular surface. Occlusion and masticatory muscles are the main drivers of the condylar position. The growth of the mandible, the dentition, and the facial skeleton are essentially due to major growth nuclei of the lower jaw, which are symmetrically located in the condyles. In particular, their superficial proliferative areas lay very close to the synovial membrane in the articular cartilage. Hence, in contrast with the peripheral joints, where the distance between the synovial membrane and the growing areas is rather wide, in TMJs, any inflammatory process of the synovium immediately affects these delicate zones, and may quickly alter the physiological growth [17–19]. Of note, the most intense mandible growth occurs in the first 6 years of age, whereas its later potential development drops to 15% up to 21 years of age. Therefore, the younger the child and the longer the period in which growth disturbance occurs, the greater the impairment of morphologic development [20].

Persistent synovitis of the TMJ in children with JIA may lead to reduced mouth opening, pain, and abnormal craniomandibular growth. When bilateral, depending on the child’s age, micrognathia, dental malocclusion, and anterior open bite are the most evident clinical features. On the contrary, unilateral involvement is responsible for facial asymmetry, as prominent as the younger the patient at its onset. Morphological alterations can be associated with muscle functional impairment and pain, resulting in difficulty with proper oral hygiene and an increased risk of dental caries [21]. Moreover, a recent wide cross-sectional study, including 3,343 children with JIA, documented that JIA patients with TMJ involvement experience higher levels of disability and disease activity, and impaired health-related quality of life (HRQOL), compared to JIA patients without TMJ involvement and healthy children [22, 23].

The complete joint examination is the essential clinical tool for the detection of joint swelling, tenderness, pain on motion, and limited range of motion in patients with JIA, and includes the evaluation of TMJs (Figure 1).

However, TMJ swelling is not clinically detectable and JIA patients rarely report complaints or present limitations of TMJ, unless at later stages. Chronic inflammation of the TMJ can result in subjective symptoms and clinical signs, such as pain on movement and upon palpation, sounds upon mouth opening like cracks and crepitations, reduced maximum interincisal opening, limited movements and jaw deviation. Mandibular growth may be unilateral or bilaterally impaired in case of affection of one or both TMJ, at a variable degree depending on the child’s age at onset of TMJ disease and TMJ disease duration, as already mentioned [24, 25].

Indices for the anamnestic dysfunction (Ai) and the clinical dysfunction (Di) were developed by Helkimo in 1974 to identify the degree of severity of TMJ dysfunction [26]. The Helkimo index consists of three different levels, corresponding to three sub-indices: the anamnesis index, derived from the history taking, with the reporting of symptoms of dysfunction in the masticatory system by the individuals; the clinical dysfunction index, which expresses the functionality of the masticatory system; and the occlusal index, which takes into account the complete analysis of the individual’s dental occlusion, with assignment of a score of 0, 1, or 5 points for number of teeth, number of teeth in occlusion, occlusal interference between centric relation and centric occlusion and joint interference.

Helkimo’s indices have seldom been used for investigating TMJ involvement in JIA patients. Some researchers applied them to study the association between initial clinical TMJ findings and the severity of TMJ involvement over time [27, 28]. Another study measured the association between clinical TMJ findings at the initial examination of JIA patients and the severity of TMJ arthritis, assessed clinically through the Helkimo’s indices and on imaging through TMJ magnetic resonance imaging (MRI) [29]. However, Helkimo’s index is considered highly subjective for two main reasons: there are no definitions for calculating the anamnesis and occlusal components of the index; the examination of the three components does not merge into a single numeric value. Hence, its interpretation and use for comparison in the same subject over time and in different subjects remain unclear [30].

Other authors explored the performance in JIA of detailed examination protocol for the detection of temporomandibular disorders (TMD), i.e., Diagnostic Criteria/Temporomandibular Disorders (DC/TMD) protocol [31, 32]. The updated protocol for children and adolescents registers the presence or absence of pain or headache in the 30 days prior to the examination and the location of pain; it includes the path of jaw opening and jaw deviation (corrected or uncorrected) in maximum opening, measure of maximum mouth opening, right laterality, left laterality, protrusion, presence of pain associated with these movements, with the specification of location (muscular, articular), pain on muscle palpation, pain and noise on joint palpation and auscultation. Maximum mouth opening is considered limited when below 36 mm in adolescents, as in adults, and < 32 mm in children. Laterality and protrusion movements can be studied only in adolescents (≥ 10 years): laterality movements are considered limited when below 8 mm, whereas protrusion movements when below 5 mm. The DC/TMD protocol is very detailed and complete, but, similarly to Helkimo’s indices, it is complex, requires specific orthodontic training, is time-consuming for completion, and does not specifically focus on orofacial manifestations of JIA [25].

In the recent years the Temporomandibular Joint Juvenile Arthritis Working Group (TMJaw), an independent group of international specialists in multiple areas, reported recommendations for standardized orofacial examination in patients with JIA that can be performed by pediatric rheumatologists as well as dentists and maxillofacial-surgeons in daily practice [33, 34]. These recommendations emphasize the importance of history taking and clinical examination, and provide clear explanation and illustration for a < 3 minutes examination (Figure 2).

The TMJaw group also provided standardized terminology, with the distinction of active inflammatory arthritis (TMJ arthritis) from damage/dysfunction resulting from previous disease (TMJ involvement) [35]. Data from a Danish JIA cohort study revealed that at least one orofacial symptom and at least one orofacial dysfunction at baseline examination similar to the proposed short screening protocol were associated with hazard ratio (HR) 2.2 and 3.3, respectively, of dentofacial deformities at 36 months follow-up [36]. Hence, this tool appears to be reliable and feasible in the routine clinical setting of different specialties.

The present perspective highlights that several international multidisciplinary initiatives provided their multifaceted efforts in early detecting TMJ arthritis in patients affected by JIA. Considering the potentially severe complications, timely diagnosis and appropriate treatment of TMJ involvement in JIA are of great importance. Currently, pharmacological treatment options for TMJ arthritis include intraarticular glucocorticoid injections (IAGI), conventional disease-modifying drugs (c-DMARDs), or biologic therapies (b-DMARDs) [54]. Physiotherapy, occlusal and distraction splints, and functional orthodontic appliances are sometimes adopted, largely depending on the interaction among the specialists and the availability of services to families [55]. Of note, TMJ IAGI are not recommended in pre-pubertal ages, whereas c-DMARDs and b-DMARDs may be indicated for concomitant involvement of other joints, independently of TMJ. Hence, in JIA patients solely treated with IAGI for oligoarthritis in joints other than TMJ or in those on treatment with c-DMARD and/or b-DMARD, TMJ arthritis may be under-investigated, and hence under-diagnosed and potentially under-treated, for both inflammatory and structural features [56, 57].

The orofacial examination has still an important role as screening for supporting indication to further investigations, which cannot be thoroughly applied for the above-mentioned limitations. The recommendation of a routine standardized orofacial examination approach is now further enhanced by the availability of consensus-based JIA-specific orofacial examination protocol, recently published [34].

Conventional radiography and CB-CT are employed to analyze condylar bone abnormalities and offer excellent resolution of cortical surfaces. Both cannot sufficiently analyze soft tissue and are associated with radiation exposure. Therefore, their use is limited to long-term monitoring of structural alterations [58, 59]. On the other side, CB-CT is considered the gold standard for assessing bony TMJ components, i.e., TMJ involvement in JIA, particularly useful when CE-MRI cannot be performed [24, 30]. OPT may still play a role in screening children with JIA, particularly at younger ages for the selection of those deserving of MRI examination.

Hitherto, CE-MRI is considered the gold standard for the complete assessment of TMJs in JIA, because of the large view of the joint and the possibility of extensive evaluation also of bones and soft tissues around the joint. Nonetheless, TMJ CE-MRI still carries some challenges in its metric properties and its findings need to be cautiously interpreted. Moreover, it is not widely available, it is costly, and it requires intravenous contrast sequences and often sedation in children. Hence, TMJ CE-MRI cannot be recommended for screening in JIA patients and can be used in selected cases.

Despite the recent dramatic advances in the applicability of MSUS in JIA [60], this imaging technique has been poorly used for TMJ assessment. The narrow acoustic window and the capability to visualize only a small superficial part of the joint represent intrinsic limitations. In addition, the lack of a standardized image acquisition technique in TMJ widens the operator dependency. Therefore, the interpretation of TMJ sonographic findings in JIA patients is controversial. Nonetheless, due to the recent technical advances in MSUS machines, the increasing availability of high-frequency probes that allow more clear and precise images of superficial structures, the reduction in the costs of US machines, and the spreading of MSUS in pediatric rheumatology, MSUS may be further explored for the assessment of TMJ in JIA [52, 61]. LPAS measured by MSUS is a candidate feasible measure of the synovial thickness of TMJ in JIA patients for early identification of TMJ arthritis.

Due to the anatomical and functional complexity of TMJs and the physiological changes that occur during growth, timely diagnosis of TMJ arthritis in JIA represents a challenge. Advances in imaging modalities and multidisciplinary international efforts are efficiently contributing to solving the limitations of each approach. Further investigations need to be kept in the next agenda for prompt, reliable, safe, and affordable screening of TMJ involvement in JIA patients. Since TMJ disease may occur initially in one joint and involve the other over time, standardization in the detection of TMJ arthritis would also allow us to better capture and understand the natural history of this joint involvement throughout the JIA disease course.

The TMJaw short screening protocol is a quick TMJ assessment in JIA patients, applicable by different specialists in the routine clinical setting. Prospective studies would allow investigation of its prognostic value in the early detection of TMJ involvement in JIA.

OPT is characterized by low radiation exposure and wide availability in dental offices; despite it provides no information on inflammatory alterations, early identification of changes in the asymmetry index may support the selection of JIA patients toward timely advanced investigations.

Though it is considered the current “gold-standard” in the assessment of TMJ arthritis, TMJ CE-MRI still carries some challenges in its metric properties. Therefore TMJ CE-MRI findings need to be cautiously interpreted. Studies on its discriminative ability and responsiveness are hampered by the lack of external measures. The minimal clinically important difference in TMJ CE-MRI findings has not been determined yet. Further development in MRI technique would maybe allow for examination without intravenous contrast agents and shorter acquisition protocols, thus enabling a wider application in younger children with JIA.

The LPAS of the TMJ in JIA measured by MSUS proved to be correlated with LPAS measured by MRI. It may represent a quickly available measure of the synovial thickness of TMJ in JIA patients. Its potential usefulness in the detection of early TMJ alterations should be further investigated.