Juvenile idiopathic arthritis (JIA) is the most common autoimmune chronic systemic disease of the connective tissue affecting individuals at the developmental age(1, 2). The term juvenile idiopathic arthritis (JIA) was introduced by the ILAR (International League of Associations for Rheumatology) to replace two other terms: juvenile rheumatoid arthritis (JRA) and juvenile chronic arthritis (JCA).
The course of JIA varies and is difficult to predict. In some patients, arthritis can be moderate, in others long-term remission is sustained and in the remaining cases, the disease is active despite treatment leading to progressive joint destruction and physical disability in 10% of children. Severe disability within the skeletal system concerns 2–5% of children(2–5). Approximately 31–55% of JIA patients enter adulthood with an active disease(6).
About 55–75% of patients with JIA present with monoarticular or pauciarticular arthritis. The most commonly affected joints include the knees (frequently monoarticular onset) followed by hands and wrists, hip, ankle and tarsal joints, more rarely tarsometatarsal joints, cervical spine or temporomandibular joints(7–9). The involvement of the wrist, ankle, hip or cervical spine is associated with more severe JIA, worse functionality and a worse response to treatment(9). Hip joint involvement, which is the main cause of disability, is observed in approximately 35% of patients(10). Total hip replacement is conducted in 26–44% of children within the first 10 years from the onset(3). Patients with polyarthritis are at the greatest risk of disease progression and joint destruction.
JIA can develop at any age in childhood. Data on its incidence are probably underestimated. Nonetheless, they indicate that the incidence of JIA in European children younger than 16 years of age is approximately 3–15 per 100000(1).
The etiopathogenesis of the disease is unknown. Genetic predisposition and environmental factors have a significant impact on its development. The genetic predisposition can be associated with sex, class 1 and 2 HLA alleles, cytokine-coding genes, adhesion molecules or signal-transmitting proteins. Environmental factors include: bacterial and viral infections as well as physical and even mental trauma, which can lead to the breaking of the immune tolerance and development of the disease in predisposed children(1, 11).
Definition and clinical picture
According to the ILAR, JIA is arthritis with the onset before the age of 16 and lasting for at least 6 weeks. Since its etiopathogenesis is unknown, the diagnosis is established on the basis of the clinical picture and once other diseases, of so-called exclusion list, are ruled out (such as infectious, reactive, allergic, toxic arthritis, arthritis accompanying other connective tissue conditions and arthropathies in the course of neoplastic, hematologic or autoimmune diseases)(1, 7, 12, 13).
Despite the fact that JIA meets the aforementioned criteria, it still remains a heterogeneous group of arthritis which has been divided into several subtypes based on prevailing clinical signs in the first 6 months from the onset and laboratory findings(1, 12, 13). These subtypes are:
systemic-onset juvenile idiopathic arthritis;
pauciarticular or oligoarticular juvenile idiopathic arthritis (oligoarthritis), including persistent or extended arthritis;
polyarticular rheumatoid factor-positive juvenile idiopathic arthritis;
polyarticular rheumatoid factor-negative juvenile idiopathic arthritis;
psoriatic juvenile idiopathic arthritis;
other types of arthritis (so-called undifferentiated forms) in which:
the clinical picture of the disease does not meet the criteria for any of the aforementioned type, or
the clinical picture combines two or more JIA types.
Below, the individual subtypes of JIA are characterized:
Systemic JIA is found in 4–20% of children with JIA(1, 5). This form develops equally frequently in boys and girls and can occur at any age. The diagnosis is established based on signs of arthritis in at least one joint with concomitant or preceding fever lasting at least 2 weeks as well as the presence of at least one of the following symptoms: evanescent and erythematous rash, generalized lymphadenopathy, hepato- or splenomegaly or serositis(1). The most common complications of this form of JIA are amyloidosis and life-threatening macrophage activation syndrome (in approximately 5–10% of cases)(1, 5, 14).
Oligoarthritis involves ≤4 joints within the first 6 months from the onset. It is found in 27–60% of children with JIA(1, 5). The knee is usually affected first followed by the ankle joint. In this case, arthritis is asymmetrical. It is characterized by early onset (<6 years of age) and occurs mainly in girls. Most patients present with positive antinuclear antibodies (ANA) (70%). Approximately 15–20% of children with this form of JIA develop uveitis (it is 6 times more common in girls), which can lead to severe vision impairment, including blindness.
Polyarticular RH-positive JIA (so-called seropositive JIA) accounts for only 2–7% of JIA(12). Clinical signs and immune disorders presented by patients with this form of JIA resemble rheumatoid arthritis in adults. It is characterized by arthritis in ≥5 joints during the first 6 months of the disease and positive IgM rheumatoid factor (RF) in the serum. This form is usually observed in girls(1). The clinical picture includes symmetrical polyarthritis in small joints of the hands and feet. Large joints, such as the knee, hip or glenohumeral, can also become affected at the beginning of the disease (approximately 1/3 of patients), but such a situation usually accompanies arthritis in small joints(1, 15). Rheumatoid nodules are present in approximately 1/3 of patients(1). This form of JIA most frequently leads to joint damage. Erosions are detected in radiographs in nearly all children during the first 5 years from the onset. They are usually observed to occur in the carpal, metacarpophalangeal (MCP), metatarsal and interphalangeal joints. Biological therapy delays this process considerably. Severe extra-articular complications of this form of JIA are rare. They include aortic insufficiency(1) and interstitial changes within the lungs. Acute or chronic uveitis develops sporadically.
Polyarticular RH-negative JIA affects older children. It is characterized by arthritis in small and large joints. The inflammatory process involves ≤5 joints within the first 6 months from the onset with negative IgM rheumatoid factor. This form is diagnosed in 11–28% of children with JIA(1). There are two incidence peaks: between the age of 2 and 4 and between the age of 6–12. Girls develop this form twice as frequently as boys. Apart from usually symmetrical arthritis in large joints and small joints of the hands and feet, general symptoms, such as: morning stiffness, slightly raised temperature, weakness or weight loss, are observed as well. Inflammatory changes in the eye are found in merely 5% of patients.
Psoriatic arthritis (PsA) mainly affects small joints of the hands and feet. It is characterized by accompanying recurrent acute uveitis in 20% of children(13). It accounts for 2–11%1 or, according to a different report, 5–7% of JIA. The ILAR states that this form can be diagnosed when arthritis occurs in conjunction with psoriatic features or psoriasis in a family member (parents, siblings), dactylitis (so-called sausage fingers) or typical nail changes (nail pitting, onycholysis or oil drop sign). At the onset, the disease is typically oligoarticular, but can develop into asymmetrical polyarthritis. Merely 10% of patients present with articular and cutaneous changes simultaneously. In a half of patients, arthritis precedes psoriasis. In the initial stages of the disease, synovitis is usually observed in the knee, ankle and metatarsophalangeal (MTP) joints and occurs in conjunction with dactylitis. Sternoclavicular joints are typically involved(5).
Enthesitis-related arthritis (ERA) constitutes 5–10% of all JIA cases. It is the only form of juvenile idiopathic arthritis found to occur mainly in boys, usually older than 6 years of age. Most patients present with positive HLA-B27 antigen. Apart from arthritis or enthesitis, the condition that must be met for ERA to be identified is the presence of at least two of the following criteria: sacroiliac tenderness on palpation or inflammatory back pain, positive HLA-B27 antigen, arthritis with onset before the age of 6, acute symptomatic uveitis, ankylosing spondylitis, arthritis with enthesitis, sacroiliitis associated with inflammatory bowel disease, reactive arthritis and uveitis in a first-degree relative. Moreover, psoriasis or its family history (in first-degree relatives) must be ruled out and IgM RF must be found negative at least twice with a 3-month interval(5). The most typical sign of this form of JIA is enthesitis, usually involving the attachment of the Achilles tendon to the calcaneal tuberosity and the attachment of the quadriceps muscle to the patella(5). Furthermore, a clinical examination usually reveals features of oligo- or polyarthritis in, among others, the hip and other joints of the lower limb(1, 13). This form of JIA can have a mild course with ≤4 affected joints. Sometimes, however, it progresses to sacroiliitis and spondylitis (30–40% of patients)(13). Although the disease mainly affects peripheral joints, it is classified as a spondyloarthropathy (spondyloarthritis).
Undifferentiated arthritis includes cases (approximately 11–21%) that do not meet the criteria for any of the aforementioned categories or meet the criteria for more than one category(1).
The classification of JIA presented above, based on the clinical picture in the first months of the disease, raises controversies and therefore attempts have been made to find other markers to define given forms. An example is the usage of antinuclear antibodies (ANA). Italian authors(16) have concluded that, by contrast with ANA (–) patients, ANA (+) ones with various types of JIA according to the ILAR classification present similar clinical features: younger age of onset, female sex, asymmetrical oligoarthritis, no involvement of the hip joint and uveitis.
Radiography is the standard modality in the assessment of JIA. However, it is capable of showing only advanced destructive changes and does not enable early detection of soft tissue inflammation, which can be observed in an ultrasound or magnetic resonance scan (which will be discussed in the second part of the publication)(2, 16, 17). Early diagnosis enables rapid implementation of treatment that can prevent serious complications in numerous patients. This mainly concerns the cervical spine, in which ankylosis develops rapidly in children, and peripheral joints, including temporomandibular joints, the involvement of which can lead to facial deformities.
Imaging in JIA begins with radiography in order to identify typical pathological changes and rule out other bone-related pathologies (cancer, trauma, developmental defects, other forms of arthritis)(8). The standard procedure involves the performance of comparative joint radiographs in two planes. Radiographic changes in JIA are observed in late stages of the disease and their progression is usually slow. The major structures assessed are bones. Radiographs can also indirectly indicate the presence of soft tissue inflammation (i.e. in joint cavities, tendons sheaths and bursae) based on the thickening and increased density of the soft tissue shadow as well as dislocation of fat folds. Signs of articular cartilage defects are also seen in radiographs indirectly – based on changes in joint space width(8).
Typical radiographic changes
Inflammatory changes in JIA usually involve(7–9):
the knee joint (frequently with monoarticular onset, which makes it necessary to differentiate with tuberculosis, proliferative process and trauma);
the joints of the wrists and hands;
the ankle and tarsal joints, more rarely MTP;
the elbow joints;
the hip joints;
the cervical spine;
the temporomandibular joints.
Radiographic changes typical of JIA include:
thickening and increased density of periarticular soft tissue shadow (Fig. 1);
periarticular osteoporosis which can be generalized in advanced forms; sometimes hypertrophic osteoporosis is observed (Fig. 2);
periosteal thickening/periosteal reaction at the metacarpal, metatarsal and phalangeal diaphyses, sometimes leading to the loss of indentation of the diaphysis; it can be the only early sign of inflammation in the course of JIA (Fig. 3);
disorders in the development and maturation of ossification centers (Fig. 3);
disorders in the shaping and development of bone epiphyses, including balloon-shaped hypertrophy ("ballooning") due to epiphyseal and growth plate congestion, as well as growth disorders referred to as rheumatoid pseudo-chondrodystrophy due to premature closure of growth plates/premature physeal fusion (Fig. 4);
tendency to fibrous and osseous ankylosis in each affected joint (Fig. 5);
typical involvement of the cervical spine which can lead to ankylosis of the intervertebral joints and sometimes suboccipital area. Hypoplasia of the vertebral bodies and intervertebral discs is observed (Fig. 6). Atlantoaxial joint involvement is not as common in children as it is in adults (subluxation in this joint or odontoid damage are then less common);
the following can be observed in large joints: swelling and increased density of periarticular soft tissue, periarticular osteoporosis, geodes and erosions, joint space narrowing and developmental disorders.
Periarticular soft tissue swelling in the right knee
Severe periarticular osteoporosis, hypertrophied epiphyses, disorders in skeletal development. Contracture in some proximal interphalangeal joints (PIP) of the hands with soft tissue swelling
Periosteal reaction in the proximal phalanges of both hands. Disorders in the development and maturation of ossification centers
Periarticular osteoporosis in the left knee joint, hypertrophy of the left femoral and tibial epiphyses, joint space narrowing of the left knee joint, particularly at the medial side
Osseous ankylosis in the fourth and fifth PIP joints of the left hand. Periarticular osteoporosis, contractures and subluxations in the distal interphalangeal joints (DIP), PIP and MCP joints of the hands. Hypoplasia of the skeletal system
Osseous ankylosis of C2–C6 intervertebral joints, osteoporosis, loss of cervical lordosis, multi-level discopathy to the C6 level
Dilemmas in radiography
Joint damage assessment in children is complicated by the growth and development of their skeletal system(18). Nonossified cartilaginous epiphyses are thicker in children and undergo changes as they grow (ossification). Except for the distal femoral epiphysis, they become thinner with age and are gradually replaced by bone tissue(7). From the age of 1, secondary ossification centers appear within the hands, including wrists, and feet (in metacarpals and metatarsals), and the whole ossification ends between the age of 12 and 22.
The pathological process in JIA disturbs skeletal development. In early childhood, delayed or accelerated appearance of ossification centers or their uneven distribution is observed. As a result, a radiograph will present a combination of the natural development and pathological changes in the skeletal system due to an ongoing inflammatory process(7, 8, 18).
The nature of bone vascularity contributes to the formation of destructive changes is children. In adults, articular cartilage is not vascularized and it protects the underlying cortical bone from inflammation in joint cavities. That is why bone erosions in adults are typically marginal, i.e. located at the border of the articular cartilage. Only at later stages, after articular cartilage is destroyed by the pannus, do they reach the subchondral layer. In children, however, bone epiphyses are vascularized and form anastomoses with metaphyseal vessels(18, 19). As a result, inflammation in children affects the epiphyseal cartilage and can spread to the ossification center, causing premature development of ossification centers in the initial stages of the disease(5, 19). The most common complication of JIA is lengthening of the lower extremity(5). Epiphyseal cartilage destruction and premature epiphyseal closure occur in the later stages of disease progression. Bone shortening, particularly in the phalanges of the hands and feet (brachydactyly), is observed more rarely(5). In radiographs, these processes are manifested by: epiphyseal overgrowth (due to their accelerated development), growth retardation and deformations (due to premature closure of growth plates and ossification inhibition)(20).
Complications of temporomandibular joint involvement may include limited mandibular mobility (opening) or micrognathia, which causes a typical bird face deformity(5). Magnetic resonance imaging is the method of choice in the diagnostic workup of early inflammatory changes(21).
Erosions (defects in the subchondral layer) are a late complication in children due to a thick layer of hyaline cartilage and the presence of non-calcified epiphyseal cartilage, which is not visible in radiography. Early destructive changes, i.e. defects in this cartilage, which are manifested by joint space narrowing, are not visible in radiography either. In order to differentiate the natural process of skeletal development from cartilage reduction caused by arthritis (erosions), joints should always be assessed symmetrically(19).
Treatment monitoring in radiography
The presence of erosions is a well-proven factor of unfavorable prognosis. That is why their assessment in the diagnostic workup is so important. Radiography is still considered the gold standard in the monitoring of JIA treatment efficacy(9). Nonetheless, it is associated with numerous limitations.
First of all, scoring methods used for adult patients (e.g. by Larsen, Steinbrocker or van der Heijde), which assess joint destruction based on the evaluation of joint space width as well as number and size of erosions, are not suitable in children(9). In contrast to adults, it is difficult to reliably assess articular cartilage thickness and the size of erosions in children by mere examination of joint space width, which narrows as the ossification process progresses(9, 19, 20). The measurement is particularly problematic in symmetrical arthritis(20).
Moreover, the disease can result in large erosions which are not visible in radiographs until ossification is complete(20).
The literature proposes a range of methods to assess the severity of inflammatory changes in radiographs in the course of JIA (see for instance: Poznanski, van Rossum et al., Rossi et al., Ravelli et al., Mallatia et al.; Greulich score and Pyle atlas(19)). The first radiological score was proposed by Poznanski in 1978. It serves for assessment and monitoring of carpal joint destruction(20). It is the ratio of the distance between the midpoint of the distal radial growth plate and the base of the third metacarpal to the length of the second metacarpal (Fig. 7). This method has been found to be reproducible in the monitoring of carpal joint destruction in all JIA types(19). However, it is limited to the wrist only and can be applied only until the growth plate closes and the development of the second metatarsal is complete. Moreover, it does not include assessment of joint space width or erosions and is difficult to apply in the case of large destructive erosive changes. As a result, it is rarely used at present(19, 20).
Measurement of the carpal joint length according to Poznanski et al.
Another system (Rossum/Dijkstra) was based on a dozen or so radiographs (of the cervical spine, mandible, shoulders, elbows, hands, sacroiliac joints, hips, knees, ankles and feet). However, this method was associated with a high level of radiation exposure, particularly of the pelvis and gonads, and is time-consuming. Furthermore, the Sharp score and simplified Larsen score have also been investigated for assessing joints of the hands and wrists in the course of JIA. Both methods showed moderate to strong correlations with the clinical assessment of disease activity(19).
Ravelli et al.(22) have adapted the Sharp/van der Heijde score for assessment of polyarticular JIA in children at the age of 5–6. It is one of the most popular scores to assess radiographs in JIA and is based on joint space width, and more specifically – on joint space narrowing (JSN), which is an indicator of damage to the hyaline cartilage and epiphysis(4). This measurement is of particular significance in children since JSN is more common in this group of patients than erosions. Moreover, erosions in children are more frequently found at sites rarely observed in adults. That is why Ravelli et al.(4) modified the Sharp/van der Heijde score by adding five additional sites in each wrist: bases of the 2nd–4th metacarpals, capitate bone and hamate bone (Fig. 8). The advancement of bone changes is assessed on a 5-grade scale(22).
Modification of Ravelli et al.; five new regions: bases of the 2nd–4th metacarpals, capitate bone and hamate bone
The first part of the publication presented the clinical classification of JIA and the radiographic picture of this disease. The second part will discuss ultrasound and magnetic resonance imaging. It must be noted that the awareness of the role of imaging in the diagnostic workup of JIA is growing among clinicians. Not only are such examinations significant for early diagnosis and monitoring of disease activity or treatment, but also for predicting treatment response or the course of the disease, confirming remission and diagnosing complications (aseptic necrosis, compression fracture of vertebral bodies). In 2015, the European League Against Rheumatism (EULAR) and Pediatric Rheumatology European Society (PReS) published a joint statement defining areas in which imaging plays a significant role in the diagnostic workup of JIA(23). Moreover, the document specified research priorities. The document was created mainly by rheumatologists and this is probably the cause why certain priorities do not appear to be innovative or do not seem to require further analyses from the point of view of diagnosticians, for example the superiority of ultrasound-guided interventions over “blind” procedures or the usage of imaging for the monitoring of treatment efficacy or visualization of features of destruction. From the radiologist's point of view, the major problem is still the differential diagnosis, particularly at early stages of the disease, and discriminating between chronic disease and its remission, which also constitutes a problem in adults.
Conflict of interest
Authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication.