Arthritis is inflammation of synovial tissue within a diarthrodial joint*. Infection-related arthritides are discussed in Chapter 152, but idiopathic arthritides constitute another group. Because the pathogenesis of the idiopathic forms is not completely understood, a variety of schemes have been devised to classify childhood arthritides according to the pattern of involvement, associated symptoms, and genetic factors. The classification criteria for juvenile idiopathic arthritis (JIA) proposed by the International League of Associations for Rheumatology is the most current,¹ and is followed in this chapter. Based on the number of inflamed joints, laboratory features, family history, and extra-articular features, seven subtypes are recognized: oligoarticular arthritis, rheumatoid factor (RF)-positive polyarthritis, RF-negative polyarthritis, systemic onset JIA, enthesitis-related arthritis (ERA), psoriatic arthritis, or undifferentiated arthritis (Table 150-1).

The diagnosis of JIA is clinical, defined as joint swelling or limitation of joint range of motion with joint pain or tenderness. These signs must be present consistently for at least 6 weeks in a patient younger than age 16 years. The annual incidence of JIA is estimated at 10 per 100,000 children, and the prevalence of JIA in the United States is about 1 in 1000 children younger than 16 years.² Estimates of the actual number of American children with JIA vary between 70,000 and 100,000, including both active and inactive cases.

Children with arthritis typically demonstrate stiffness after prolonged periods of inactivity, such as upon arising in the morning or after naps, long car rides, or sitting in class at school. Conversely, children with arthritis typically feel better after a warm bath or several minutes of activity. Cold, damp weather or swimming in cool water tends to be more difficult for children with arthritis, whereas warm weather generally relieves symptoms. Thus a child with arthritis may suffer joint stiffness in the morning but may be quite comfortable exercising strenuously later in the day. Pain is an unusual complaint in a child with JIA, and nighttime awakening is uncommon as well.³

Systemic-onset JIA, or Still’s disease, accounts for about 10% to 15% of all children with JIA. This is the subtype of JIA that most closely resembles an infectious disease. Although systemic-onset JIA can occur at any age, the peak age of onset is between 1 and 6 years. Boys and girls are equally affected. As its name implies, this is a systemic illness characterized by fever, rash, and arthritis. These children are often admitted to the hospital for evaluation of fever of unknown origin. The fever of systemic-onset JIA is described as quotidian or double quotidian; children typically have one or two spikes of fever greater than 39°C at about the same time every day. In between episodes of fever, the temperature returns to the baseline level or lower. The fever must be present for at least 2 weeks to be considered a diagnostic criterion. The rash of systemic-onset JIA is salmon pink, transient (lasting minutes to a few hours), nonpruritic, and migratory. It consists of discrete macules 2 to 5 mm in size, mostly on the trunk and proximal extremities. The rash often accompanies fever spikes, and it is typically seen after a shower. Rubbing or lightly scratching the skin elicits erythema (Koebner phenomenon) and might be followed by the appearance of transient macular lesions. Fever and rash are found in systemic-onset JIA but are not part of the clinical picture of other subtypes of JIA. These symptoms may precede the onset of arthritis by days to months. Most children with systemic-onset JIA develop chronic polyarthritis over time. Joint involvement is variable at disease onset, with anywhere from no joints to numerous joints being involved. Children with systemic-onset JIA also have laboratory evidence of systemic inflammation. The white blood cell count is usually elevated, with a predominance of neutrophils, accompanied by anemia and thrombocytosis; the erythrocyte sedimentation rate (ESR) is moderately to significantly elevated. Hepatosplenomegaly, lymphadenopathy, and serositis can also be seen in systemic-onset JIA.

Polyarticular JIA is characterized by the presence of arthritis of at least 6 weeks’ duration in five or more joints. Polyarticular JIA accounts for 30% to 40% of cases of JIA and typically affects more girls than boys. Two distinct subtypes are recognized, based on the presence or absence of rheumatoid factor (RF). If the onset occurs during the first peak, at age 1 to 3 years, patients are generally RF negative. Girls affected during the second peak, just before puberty, have a disease that is more like adult rheumatoid arthritis, are RF positive, and have early erosions and often subcutaneous nodules. In both types of polyarticular JIA, the onset is generally insidious, with children gradually accruing additional swollen joints over time. Typically, the arthritis is symmetrical above and below the waist and between the left and right sides, and it often involves the small joints of the hands and feet. Fever is generally absent, but children may complain of fatigue, malaise, and anorexia. Polyarticular JIA may be accompanied by mild anemia and a modest elevation of the ESR. Synovitis in multiple joints may lead to chronic joint changes and bony erosions. Up to 50% of those with polyarticular JIA show radiographic abnormalities within 2 years of onset if not treated aggressively.

Oligoarticular JIA, the most common type, accounts for about 40% of all children with JIA. It is characterized by the presence of arthritis in four or fewer joints during the first 6 months of disease. Oligoarticular JIA is more common in girls, and the onset age peaks between 2 to 4 years. Large joints are often involved, with the knee being most commonly affected. The arthritis can be asymmetric, and often only one joint is affected at presentation. Inflammatory markers are often normal or mildly increased. Antinuclear antibodies (ANAs) are detected in about 60% of patients with oligoarticular JIA. The International League of Associations for Rheumatology (ILAR) classification distinguishes two subcategories of oligoarticular JIA depending on the number of joints involved after the first 6 months of disease. In persistent oligoarthritis, the arthritis is limited to four or fewer joints, and in extended oligoarthritis, the arthritis extends to more than four joints. About one-third of children with oligoarticular JIA go on to have extended oligoarthritis. In younger children, oligoarticular JIA often presents insidiously with refusal to walk or a limp in the morning that typically improves as the day goes on. Children seldom complain of pain, although parents may notice swelling of a knee or other large joint. This type has relatively few systemic signs such as fever.

Enthesitis-related arthritis (ERA), affects ~10% of children with JIA. This subtype is characterized by arthritis and enthesitis (inflammation of tendon and ligament attachments). Most often the heels and knees are involved with enthesitis. The arthritis is more likely to involve the lower extremities. Inflammatory spinal pain and sacroiliac joint involvement can also be seen with this subtype. ERA typically affects boys after the age of 6. Most children are also positive for HLA-B27. In some cases, children present with just arthritis but have a positive family history of spondyloarthropathies in a first-degree relative. Children with ERA are at risk for painful acute anterior uveitis.

Psoriatic arthritis is characterized by the presence of arthritis and psoriasis. In children without a characteristic rash of psoriasis, the diagnosis requires any two of the following: family history of psoriasis in a first-degree relative, dactylitis (swelling of a digit extending beyond joint margins), and nail pitting or onycholysis. Psoriatic arthritis comprises 2% to 11% of all JIA. There is a biphasic distribution, with an early peak at 2 to 4 years and a later one at 9 to 11 years. This subtype is more common in girls. Chronic asymptomatic uveitis can be seen with this subtype.

Undifferentiated arthritis includes patients with JIA who do not satisfy criteria for inclusion in any of the other categories, or fulfill criteria for more than one category. As such, they do not have a characteristic pattern of arthritis. The ILAR criteria define several stringent exclusion criteria, which make it difficult to accurately classify some children with chronic arthritis. For instance, a child with an oligoarticular presentation who has two positive tests for RF, or systemic JIA in a boy after the age of 6, can result in a child being placed in the “undifferentiated” category. Clinical management depends on the features of the disease in an individual patient.

Macrophage activation syndrome (MAS) is rare, but it is the one complication of systemic JIA that is most likely to cause significant morbidity or mortality. It is discussed more fully in Chapter 151. MAS resembles hemophagocytic lymphohistiocytosis, which occurs as a familial form as a result of genetic abnormalities in natural killer T lymphocytes. It also occurs sporadically as a complication of malignancy or infection.⁴ In systemic-onset JIA, MAS most commonly occurs during the first 6 months of disease, during periods of active systemic inflammation that are often associated with a change in medication. MAS manifests as unremitting fever, unlike the spiking fevers of the underlying illness. Children may demonstrate bruising and mucosal bleeding from the consumptive coagulopathy seen in MAS, as well as mental status changes, hepatosplenomegaly, and diffuse lymphadenopathy. Activation of macrophages results in phagocytosis of erythrocytes, platelets, and leukocytes, so MAS should be suspected when patients with JIA present with a sudden drop in platelets, hematocrit, and white blood cells accompanied by an elevation of hepatic transaminases. Laboratory studies also demonstrate elevated triglycerides, ferritin, D-dimers, prothrombin time and partial thromboplastin time, and a fall in fibrinogen, ESR, and serum albumin. Other subtypes of JIA are not usually associated with MAS.

Pericarditis is seen in about 3% to 9% of children with JIA, almost always in association with systemic-onset JIA. Older children are more likely to develop pericarditis, which may present as precordial chest pain, dyspnea, or discomfort referred to the back, shoulder, or neck, or it may be noted incidentally on chest imaging. Physical examination findings include tachycardia, cardiomegaly, or a pericardial friction rub at the lower left sternal border. Cardiac tamponade is a rare but serious complication of constrictive pericarditis. It is characterized by venous distention, hepatomegaly, and peripheral edema. Urgent evaluation and management are necessary to avoid progressive cardiovascular instability. JIA seldom causes parenchymal lung disease, but pleuritic chest pain due to a pleural effusion may accompany pericarditis or occur in isolation.

Anterior uveitis, or iridocyclitis, is a well-recognized and potentially serious complication of JIA. Uveitis in JIA is usually asymptomatic and chronic; it is most common in children with oligoarticular JIA (approximately 10%) and to a lesser extent RF-negative polyarticular JIA. A younger age, female gender, and positive ANA test increase the risk of iritis in most studies, although boys are at risk as well. Uveitis is rare in systemic-onset JIA, occurring in less than 1% of cases. Acute uveitis, accompanied by pain and redness, may be associated with ERA. The detection of acute uveitis in a child suspected of having systemic-onset JIA should prompt a consideration of other causes of fever and rash, such as Kawasaki disease and acute viral infections.