Chapter 46 Juvenile Rheumatoid Arthritis
PATHOPHYSIOLOGY
Juvenile rheumatoid arthritis (JRA) is a chronic autoimmune disease that begins before 16 years of age. It is the most common rheumatic disease in children and is a leading cause of short- and long-term disability. It is also a major cause of eye disease leading to blindness. Although its exact etiology is unknown, it is immune-mediated, with abnormal cytokine production in the inflammatory pathway (increased tumor necrosis factor, interleukin-1 and interleukin-6). There are also genetic predispositions, as well as environmental triggers such as infection, trauma, or stress. JRA causes chronic inflammation of the synovium with joint effusion, which can result in eventual erosion and destruction of the articular cartilage. If the process persists long enough, adhesions between the joint surfaces and ankylosis of the joints develop.
The diagnosis is based on the following criteria defined by the American College of Rheumatology:
1. The age at onset must be less than 16 years.
2. Objective evidence of arthritis must be present (defined as swelling or effusion, or presence of two or more of the following: limitation of range of motion, tenderness or pain on motion, and increased heat) in one or more joints.
3. The duration of the disease is 6 weeks or longer.
4. The onset type is defined by the type of disease in the first 6 months:
Common characteristics of JRA include morning stiffness, joint pain, limping gait, fatigue, anorexia, anemia, and weight loss.
INCIDENCE
1. JRA is twice as common in girls.
2. The incidence of JRA varies from 2 to 20 in 100,000 per year. Prevalence is about 1 per 1000 children.
3. Age ranges of peak incidence are 1 to 3 years and 8 to 11 years.
4. Subtype frequencies are systemic, 10%; polyarticular, 30%; and pauciarticular, 60%.
CLINICAL MANIFESTATIONS
Systemic JRA
1. Systemic JRA is characterized by persistent, intermittent (quotidian) fever: daily or twice-daily temperature elevations to 102.2° F (39° C) or higher, with rapid return to normal temperature between fever spikes. The fever is usually present in the late afternoon to evening. It almost always occurs with the rheumatoid rash.
2. The rheumatoid rash is described as salmon-pink erythematous macules on the trunk and extremities. The rash is migratory and in 5% of cases is reported to be pruritic.
3. Arthritis may not occur until weeks or months after the onset of the symptoms.
4. It affects 10% of all JRA patients, with peak onset from 1 to 5 years of age.
5. The arthritis pattern may be pauciarticular (one to four joints affected) or polyarticular (five or more joints affected). Those children with polyarthritis have a tendency for erosions and a poorer prognosis.
6. Extraarticular symptoms are present, including hepatosplenomegaly, lymphadenopathy, pericarditis, and pleuritis.
Polyarticular JRA
1. Arthritis is present in five or more joints in the first 6 months of disease.
2. Peak age of onset is between ages 1 and 4 years, and between 6 and 12 years.
3. Systemic manifestations include low-grade fever, fatigue, anorexia, growth failure, and weight loss.
4. Morning stiffness, gelling or stiffness after inactivity, joint pain, and sluggishness with movement are characteristic.
5. Joint involvement is generally symmetric and usually involves the large joints of the knees, the wrists, the elbows, and the ankles. The small joints of the hands and the feet may also be affected.
6. The cervical spine and the temporomandibular joints are often involved.
7. If the temporomandibular joint is involved, impaired biting, shortness of the mandible, and micrognathia may result.
8. Those with onset in late childhood or adolescence who are rheumatoid factor–positive tend to have a more severe disease course than those who are rheumatoid factor–negative.
9. Rheumatoid nodules occur in 5% to 10% of children with JRA, but are most often seen in those with polyarticular disease who are rheumatoid factor–positive. The typical rheumatoid nodule is firm, movable, and nontender. They usually occur below the elbow or at other pressure points.
Pauciarticular JRA
1. Arthritis is present in one to four joints in the first 6 months of disease.
2. Pauciarticular-onset JRA primarily affects girls, aged 2 to 4 years.
3. The joints most commonly affected are the knees and the ankles.
4. The affected joints are swollen and warm, but usually not painful or tender.
5. Uveitis (15% to 20% of cases) is insidious and often asymptomatic.
6. Disease course is variable. After the first 6 months, 5% to 10% develop a polyarticular disease course.
COMPLICATIONS
1. Uveitis is intraocular inflammation of the iris and the ciliary body, found in 15% to 20% of children with pauciarticular-onset JRA, in 5% of those with polyarticular-onset JRA, and rarely in children with systemic-onset JRA. At increased risk for development of uveitis are girls with pauciarticular-onset disease. Those with a positive antinuclear antibody are at even higher risk. The onset is usually insidious and asymptomatic; however, approximately half of children have some symptoms (pain, redness, headache, photophobia, change in vision) later in the disease course. If not diagnosed early, the disease can result in cataracts, glaucoma, visual loss, and blindness. If the disease is detected early, the prognosis is improved. In about half of all patients with uveitis, it occurs before the arthritis is diagnosed, at the time of diagnosis or soon after. In 70% to 80% of children, the uveitis is bilateral.
3. Growth disturbances, including leg length discrepancy and micrognathia
4. Valgus deformity, cervical spine ankylosis
6. Cardiopulmonary complications and other systemic complications
7. Severe anemia and malnutrition
8. Renal, bone marrow, gastrointestinal, and liver toxicity to drugs
9. Macrophage activation syndrome is a rare but severe complication of systemic JRA leading to severe morbidity and sometimes death. The syndrome is characterized by rapid development of fever, hepatosplenomegaly, lymphadenopathy, and liver failure with encephalopathy, purpura, bruising, and mucosal bleeding. A bone marrow aspiration showing active phagocytosis of red cells and white cells by macrophages and histiocytes confirms the diagnosis.
