juvenile idiopathic arthritis juvenile idiopathic arthritis juvenile idiopathic arthritis (jia) is the most common, chronic rheumatic disease of childhood, affecting approximately 16 to 150 out of 100,000 children. juvenile, in this context, refers to disease onset before 16 years of age, while idiopathic refers to a condition with no defined cause, and arthritis is inflammation within the joint. this article does not deal with the more general topic of childhood arthritis. juvenile idiopathic arthritisother namesjuvenile rheumatoid arthritisspecialtyrheumatologyfrequency16-150 in 100,000 jia is an autoimmune, noninfective, inflammatory joint disease, the cause of which remains poorly understood. it is characterised by chronic joint inflammation. jia is a subset of childhood arthritis, but unlike other, more transient forms of childhood arthritis, jia persists for at least six weeks, and in some children is a lifelong condition. it differs significantly from forms of arthritis commonly seen in adults (osteoarthritis, rheumatoid arthritis), in terms of cause, disease associations, and prognosis. the prognosis for children with jia has improved dramatically over recent decades, particularly with the introduction of biological therapies and a shift towards more aggressive treatment strategies. jia treatment aims for normal physical and psychosocial functioning, which is an achievable goal for some children with this condition. signs and symptoms arthritis means inflammation within the joint, and is usually recognised by swelling, pain, stiffness and restricted joint movement. symptoms of jia vary from individual to individual. this is mainly because jia is an umbrella term for several subtypes of jia, which differ according to the number of affected joints, severity of disease and presence or absence of inflammation in other parts of the body. the key clinical feature in jia is persistent swelling of the affected joints. any joint can be affected, but large joints such as the knee and ankle are most commonly involved. involvement of small joints of the hands and feet is more likely when many joints are affected ('polyarthritis'). swollen joints may also feel warmer to touch. swelling may be difficult to detect clinically, especially for joints such as those of the spine, sacroiliac joints, shoulder, hip, and jaw; imaging techniques such as ultrasound or mri can be very useful to identify the inflammation. joint pain is an important symptom, although some children experience minimal or no pain with their arthritis. in these children, the first sign of arthritis may be limping, especially in the morning. young children are often very good at changing how they move when they have joint pain: they learn to move so that it does not hurt. for example, a child will not push up using an inflamed wrist when climbing, instead putting their weight through the forearm. morning stiffness that improves later in the day is a common feature (this implies inflammatory-type joint pain versus mechanical-type joint pain). swelling and pain usually result in limited movement of the affected joints, for example a knee held bent causing a limp, or being unable to make a full fist. limited movement may reduce a child's ability to fully participate in activities and undertake usual tasks such as those used for self-care. in some jia subtypes, more non-specific symptoms of being unwell may be present, such as lethargy, fatigue and poor appetite. children with systemic jia usually present with fever and a classic rash and may become quite ill. late effects of arthritis can include joint contractures (stiff, bent joints with loss of movement) due to joint damage; limb length discrepancies and muscle wasting. children with jia vary in the degree to which they are affected by particular symptoms. extra-articular eye disease: jia is associated with inflammation in the front of the eye (specifically iridocyclitis, a form of chronic anterior uveitis), which affects about one in six children with jia. eye involvement occurs most commonly in girls, those with only a few joints involved (oligoarthritis), and those with a positive anti-nuclear antibody (ana). it usually follows the onset of arthritis or may be detected at the same time as arthritis; occasionally it may occur before joint involvement. the factors linking eye and joint disease are not clearly understood, and the two do not necessarily follow the same course. this complication is usually asymptomatic (without symptoms) and can occur when the joints are not active. it can be detected by an experienced optometrist or ophthalmologist using a slit lamp to look for inflammatory cells in the fluid inside the eye. most children with jia will require referral for regular slit lamp screening examinations. poorly controlled chronic anterior uveitis may result in permanent eye damage, including blindness. systemic jia: children with the systemic jia subtype often experience extra-articular manifestations including fever, rash, enlarged lymph nodes, enlarged liver or spleen, serositis and anaemia. complications jia is a chronic disorder, which if neglected, can lead to serious complications. however, with regular follow-up and modern treatments, complications have reduced and outcomes improved. if inflammation is not treated, it can damage the joint, the cartilage and the bone. with the advent of modern therapies, these complications of jia have become much less common. children with jia may have a reduced overall rate of growth, especially if the disease involves many joints or other body systems. this may be due to a combination of the disease itself, as well as its treatments, particularly corticosteroid use. paradoxically, limbs where a large joint (such as the knee) is inflamed may have increased growth in the short term, leading to limb-length discrepancy (i.e. one arm or leg is slightly longer than the other). this is due to increased blood supply to the bony growth plates surrounding the inflamed joints. bone density and bone strength may be reduced through a combination of inflammation, corticosteroid use and reduced physical activity levels. other musculoskeletal complications may include joint contractures, muscle weakness or muscle wasting. uveitis, if left untreated, can result in scarring, glaucoma, cataracts, and even blindness. regular monitoring allows for early detection and treatment. steroid eye drops are usually the first line treatment for anterior uveitis. however, other treatments – many of which also treat arthritis (e.g. methotrexate, biologics) – may be required to keep the inflammation under control, and to minimise steroid use over the longer term. long term steroid use can cause contribute to the development of cataracts. macrophage activation syndrome (mas) is a severe, potentially life-threatening complication that can occur in patients with the systemic subtype of jia. mas involves uncontrolled activation of the immune system, sometimes referred to as a 'cytokine storm', which can present with a sepsis-like picture of fever, rash, enlarged liver and spleen, enlarged lymph nodes and cardiorespiratory compromise. it is recognised by a series of characteristic changes in laboratory parameters, including a high ferritin and a paradoxically low erythrocyte sedimentation rate. causes the cause of jia remains unknown. however, the disorder is autoimmune — meaning that the body's own immune system starts to attack and destroy cells and tissues (particularly in the joints) for no apparent reason. the immune system is thought to be provoked by changes in the environment, in combination with mutations in many associated genes and/or other causes of differential expression of genes. experimental studies have shown that certain mutated viruses may be able to trigger jia. the disease appears to be more common in girls, and is most common in caucasians. the cause of jia, as the word "idiopathic" suggests, is unknown and an area of active research. current understanding of jia suggests that it arises in a genetically susceptible individual due to environmental factors. diagnosis the diagnosis of jia can be difficult, in part because joint pain in children is so common and may be from many causes other than jia. the characteristic feature of arthritis is joint swelling which is sometimes – but not always – associated with pain. the presence of joint stiffness is another typical feature, particularly when present in the morning and improving with activity. no single test can confirm a diagnosis of jia: a combination of presenting signs and symptoms, blood tests, and if necessary medical imaging, is used to make the diagnosis. the blood tests may measure levels of inflammatory markers, as well as the presence of specific immune markers which may include anti-nuclear antibody, hla-b27, rheumatoid factor and anti–citrullinated protein antibody. these serological markers may be negative in children with jia, and are often present in healthy children; as such they should not be interpreted in isolation but in the context of the clinical presentation. many children with jia have normal blood work. x-rays may be required to ensure that the joint pain and swelling is not from a fracture, cancer, infection, or congenital abnormality. in some cases, fluid from the joint can be aspirated and analysed to assist in making a diagnosis. this test can assist by ruling out other causes of arthritis such as infection. classification the current classification system by the international league of associations for rheumatology (ilar) recognizes seven distinct subtypes of jia, based on their presentation within the first six months: each subtype has a specific pattern of features as outlined in the table and descriptions below. (the seventh category, not included in the table, is 'undifferentiated' and includes any patient with jia who does not meet criteria for other subtypes, or who meets criteria for two or more subtypes). oligoarticularpolyarticular (rf negative)polyarticular (rf positive)systemic onsetpsoriaticenthesitis related arthritis % of jia50-6020-305-1010-205-1515 gender (f:m)4:14:19:11:13:21:9 typical age of onset (years)2-12 (peak 2–3)2-12 (peak 2–3)adolescenceanymid childhoodadolescence joint patternasymmetric; often large joints (knee, ankle, wrist, elbow) often asymmetric; multiple small and large joints symmetric; multiple small and large joints symmetric; multiple small and large jointsasymmetric; small and large joints including hips and especially dipsasymmetric; large joints; axial skeleton extra-articular involvementuveitis in 20%painless uveitis (especially if ana positive) rheumatoid nodulesfever, rash, lymphadenopathy, enlarged liver and spleen, serositis psoriasis, nail pitting, dactylitis, uveitis in 10%, enthesitis symptomatic uveitis in 20%, enthesitis, ibd, aortitis oligoarticular arthritis oligoarticular (or pauciarticular) jia is the most common jia subtype, and occurs when there are up to four joints involved during the first six months of disease. two subtypes of oligoarticular arthritis exist: persistent oligoarthritis, where no more than four joints are affected throughout the whole disease course; and extended oligoarthritis, where more than four joints are affected after the first six months of disease. patients in this subtype are often young, typically aged two to three years and with a female preponderance. the most commonly involved joint is the knee, but other affected joints may include the ankles, wrists, elbows and others. the anti-nuclear antigen (ana) is positive in up to 80% of patients with oligoarthritis and is associated with a higher risk of associated eye disease (uveitis), particularly in younger patients. the prefixes oligo- and pauci- mean 'few'. differential diagnosis there are several other disorders and diseases that present with symptoms like jia. these causes include, but are not limited to, infectious (for example septic arthritis or osteomyelitis) and post-infectious conditions (reactive arthritis, acute rheumatic fever, and in some geographic areas lyme disease); hematologic and neoplastic diseases such as leukemia or bony tumors; and other connective tissue diseases (such as systemic lupus erythematosus). for the systemic-onset form of jia, the differential diagnosis also includes kawasaki disease and periodic fever syndromes. some genetic skeletal dysplasias as forms of mucopolysaccharidosis especially type1 scheie syndrome, progressive pseudorheumatoid dysplasia and multicentric osteolysis, nodulosis, and arthropathy syndrome may also mimic jia, as they may present with joint swelling, joint restriction, stiffness, and pain. the clinical and radiologic overlap between genetic skeletal dysplasias and jia can be great that molecular analysis may be need to confirm the diagnosis. rarely, metabolic diseases, such as farber disease may also mimic jia. patients with farber disease typically have subcutaneous nodules and a hoarse or weak voice due to growth of nodules on the larynx. treatment the major emphasis of the treatment of jia is helping the child or young person regain normal levels of physical and social functioning by controlling inflammation and extra-articular symptoms. clinical remission should be the primary target for all patients and treatment should be adjusted until this is achieved. prompt recognition and management is important as early initiation of therapy increases the likelihood of a response to first-line treatments and of achieving drug-free remission later in life. while overarching consensus treatment guidelines exist, all treatments should be specifically