The International League of Associations of Rheumatology has classified JRA into six distinct patterns that vary by clinical presentation and evolution of symptoms, laboratory implications, potential complications, and therapeutic options. While some similarities exist among these diseases, the uniqueness of each manifestation of JRA is strong enough to justify the breakdown into the six patterns. One characteristic common to all six forms of JRA is that of “morning stiffness” that improves during the day as more movement is done. Likewise, spontaneous patterns of worsening and lessening of symptoms (which may be independent of therapy) is characteristic.
1. Systemic onset JRA: By definition, systemic onset JRA must have arthritis (swelling, pain, and warmth) of one or more joints associated with a minimum of two weeks of daily spiking fevers. The fever is often greater than 102 F (39 C) and usually spikes once or twice a day and may have the unique pattern of returning to below normal between rises. In addition, a characteristic intermittent salmon-colored rash; swollen lymph nodes, liver, and spleen; and inflammation of the lungs, the pericardium (the “sack” surrounding the heart), and other organs may occur. During febrile episodes, children appear moderately sick, but with resolution of fever they are much improved. Systemic onset JRA affects approximately 10%-15% all children suffering from JRA. There is no gender preference (the frequency in boys and girls is equal), with symptoms generally starting between 3-5 years of age. There is no unique laboratory test for JRA, but children typically have anemia and elevation of white blood cell and platelet counts, as well as alterations of general markers of inflammation. Complications of systemic onset JRA may include slower than expected growth, weakening of bones, abnormalities of liver and lung function, and consequences of therapy (see below). The prognosis is generally noted to depend upon the severity of arthritis with many/most of the systemic symptoms resolving over months to years. The low mortality rate (<0.3% in North America) is reassuring. Since the diagnosis of systemic onset of JRA is one of exclusion, the possibility of infection, malignancy, collagen vascular disease, and rheumatic fever must also be considered.
2. Oligoarticular JRA: Oligoarticular is defined as arthritis that affects four or fewer joints in the first six months of the disease. This form of JRA accounts for about 50% of all cases of pediatric chronic arthritis and may be subdivided into two groups. One group consists of those children who continue throughout the entire course of their disease having four or fewer joints involved. The other group eventually develops greater than four-joint involvement after the first six months of illness. The onset of disease is between 2-4 years of age with a female gender bias of approximately 3:1. Children with oligoarticular JRA most commonly have a single large joint (knee in approximately 90% of cases) involvement. Symptoms of joint pain and tenderness are worse in the morning in association with the previously described morning stiffness (see systemic onset JRA). The primary complication of oligoarticular JRA is inflammation of the iris (the colored region of the eye). Iritis is found in approximately 15%-20% with this form of JRA and is often without symptoms. Complications of iritis may include clouding of the cornea (cataracts), glaucoma, and vision loss. Since outcome is linked to early diagnosis, it is imperative an ophthalmologist evaluate children with oligoarticular JRA every three to four months. Conditions that should be eliminated prior to establishing a diagnosis of oligoarticular JRA include trauma, infection, malignancy, and arthritis following an infection.
3. Polyarticular juvenile rheumatoid arthritis: Children who have five or more joints involved with arthritis during the first six months of their disease are classified into the polyarticular JRA form of illness. Two subgroups of polyarticular JRA exist based upon a constellation of various laboratory studies. One group (rheumatoid factor “RF” positive) affects between 5%-10% of all patients with JRA. Late childhood through young teenage girls are the most likely to develop this pattern. Generally, small joints (such as the hands and feet) tend to be involved, and a more aggressive course has been observed. “RF negative” polyarticular JRA affected individuals tend to have a milder course and thus a better outcome. Fatigue, anemia, suboptimal growth, and iritis (to a lesser degree than oligoarticular JRA) are complications. Other conditions that must be considered and eliminated prior to establishing the diagnosis of polyarticular JRA include infection, malignancy, and collagen vascular disease (including systemic lupus erythematosus).
4. Psoriatic arthritis (PsA): Establishing the diagnosis of psoriatic arthritis involves demonstration of both large and small joint arthritis and a characteristic rash (psoriasis). Should the rash not be present, two of the following must exist: (a) family history of psoriasis in an immediate family member, (b) diffuse swelling of the fingers, and (c) pitting of the nails. Children with psoriatic arthritis may also develop iritis and should have ophthalmologic evaluation every six months.
5. Enthesitis-related arthritis (ERA): Enthesitis (inflammation at the site of tendon insertion on the bone) most profoundly affects males over 8 years of age and often involves the lower back, sacroiliac joints, and joints of the legs, ankles, and feet. Patients with a particular genetic marker (HLA-B27) may also develop iritis, inflammatory bowel disease, psoriasis, and/or ankylosing spondylitis (inflammation of the pelvic joints — most commonly the sacroiliac region). The male to female ratio is 7:1.
6. Undifferentiated arthritis: Children who either do not fit clearly into the above unique subtypes of JRA or who have symptoms/laboratory studies that overlap more than one subtype are classified as having undifferentiated arthritis. By their nature, the patient population with this form of JRA often presents with nonclassical history and/or findings on physical exam and laboratory studies. Providing an accurate prognosis and developing a treatment program are challenges.