Appendix A:  The Pediatric Rheumatic Diseases

Juvenile Rheumatoid Arthritis (JRA)

JRA, which is a unique clinical entity and distinct from rheumatoid arthritis, affects 148-167 per 100,000 children; ⁶⁸ it is the most common cause of acquired disability in children.  In JRA, the overall inflammatory process causes swelling of joints and is often accompanied by pain, rash, and loss of mobility.  The disease is classified into three types:  pauciarticular onset, polyarticular onset, and systemic onset, each with its own set of symptoms and prognoses.  

Subtypes

Pauciarticular

Pauciarticular onset, or oligoarticular onset, is the most common form of JRA  accounting for 35 percent to 50 percent of all JRA cases. ⁶⁸  By definition, pauciarticular JRA affects four or fewer joints and is most often limited to the larger joint---the knee, elbow, or ankle. ⁶⁸  The effects of this form are usually asymmetrical and symptoms include swelling of the affected joints, stiffness, and mild pain.  The peak age for diagnosis is between 1 and 3 years of age; it affects females more commonly than males, the ratio of females to males being 4-5:1. ⁶⁸   

In addition to joint inflammation, in approximately 10-20 percent of the cases pauciarticular JRA is associated with anterior uveitis (i.e., inflammation of the anterior portion of the uveal tract of the eye).  Uveitis most often occurs in patients who develop pauciarticular JRA before the age of 2 and who are ANA positive (i.e., their blood tests positive for antinuclear antibodies).  Symptoms of uveitis may occur for many years after the joint-related symptoms of JRA have remitted and may be relapsing or chronic. ⁶⁸  Patients who fit this classification should be monitored regularly by an ophthalmologist who is familiar with the effects of JRA. ⁶⁸  

The prognosis of pauciarticular JRA is the most favorable of all three forms infrequently resulting in permanent disability or joint damage.  However, 10-20 percent children with pauciarticular onset go on to develop polyarticular JRA (i.e., arthritis that affects five or more joints), sometimes called extended oligoarticular JRA.  Long term sequelea of pauciarticular JRA are more common for those who develop the disease at a younger age. ⁶⁹ For those who develop chronic uveitis, vision problems may persist for many years after joint inflammation has subsided and permanent eye damage may occur.  

Polyarticular

Polyarticular juvenile rheumatoid arthritis affects five or more joints; the overall symptoms are similar to those of adult rheumatoid arthritis.  About 40 percent of children with JRA have this form, with girls accounting for approximately 80 percent of cases. ⁶⁸  It occurs in two peaks, early childhood and adolescence.  While it typically affects the small joints in the hands, it can also affect larger joints or the knee, ankle, hips, neck, and jaw.  Polyarticular JRA is a symmetrical form of arthritis and can potentially inhibit growth in affected joints.  Many children experience, for example, retarded growth of their temporomandibular joint (TMJ), which causes pain while chewing and brushing; this can lead to decreased appetite and dental problems. 

Other symptoms of polyarticular JRA can include low-grade fever, anemia, and inflammation of internal organs.  Chronic uveitis, occurring in 10 percent of children, is less common in children with this form of JRA. ⁶⁸  The prognosis of this form is dependent on the number joints affected and the degree of inflammation.  The disease manifestations of polyarticular JRA often continue into adulthood and, similar to pauciarticular JRA, those who experience onset at an earlier age are more likely to see a longer duration of the disease. ⁶⁹  

Systemic Onset

Systemic onset JRA is the least common, but most virulent, form of JRA; it affects between 10 and 20 percent of children with JRA and strikes boys and girls at equal rates. ⁶⁸  The most common symptoms include persistent high-grade fevers, rash, and arthritis of multiple joints.  Systemic onset JRA can also cause inflammation of the outer lining of the internal organs (most often the heart and lungs), anemia, high white blood cell and platelet counts, and enlarged lymph nodes, liver, or spleen.  Macrophage activation syndrome is an uncommon and potentially fatal complication; uveitis is uncommon with systemic onset JRA.

The prognosis of systemic onset JRA varies widely.  One study shows that, unlike pauciarticular and polyarticular JRA, younger age at onset appears to indicate a shorter duration of active disease. ⁶⁹  Some cases remit within one year but recurrent flare-ups are common.  Up to 30 percent of cases disappear completely with no long-term effects, but approximately one-half of cases worsen with time and are marked by increasingly destructive arthritis. ⁶⁸

Table A.1: Characteristics of Juvenile Rheumatoid Arthritis Subtypes

Other Pediatric Rheumatology Diseases

Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune disease that typically affects the joints, skin, kidneys, heart, lungs, blood, and central nervous system.  Symptoms vary greatly across individuals, ranging from fatigue, high fever, skin rashes, and swollen joints to kidney failure, seizures, and cardiac and lung disease.  The Lupus Foundation of America estimates that approximately 1.4 million Americans have some form of the disease. ⁷⁰  More than 85 percent of patients are women and SLE is most common among minorities, with African American women experiencing the highest incidence. ⁷¹  While it is rare for lupus to be diagnosed in pre-pubescent individuals, the Arthritis Foundation estimates that in the United States approximately 25,000 children and adolescents have the disease. ⁷²   There are three other less severe types of lupus: discoid lupus erythematosus, drug-induced lupus, and neonatal lupus, the rare form that affects newborns of women with lupus. 

The overall prognosis for SLE is improving over time with 5-year survival rates increasing from 50 percent in 1950 to 80-90 percent in the 1990s; ⁷³ some statistics now show the 10-year survival rate at 90 percent, which is believed to be a result of improved medical care. ⁶⁸  The treatment of SLE involves the use of NSAIDs, corticosteroids, antimalarials, and immunomodulating drugs.  The side effects of some of the drugs can be serious, including weight gain, osteoporosis, anemia, high blood pressure, and immunosuppression, which increase susceptibility to infections.  Immunosuppression is a particularly vexing problem as several studies have found infection to be the most common cause of death in SLE. ^{74, 75}  Much like children with JRA, children affected by lupus require close medical supervision to monitor medication side effects and disease flares and access to a continuum of collaborative care across several areas of medicine, including nephrology, cardiology, and others.

Other Diseases

There are dozens of rare rheumatic diseases that can affect children.  A few of the more common kinds are:

• Juvenile Psoriatic Arthritis – characterized by nail pitting, psoriatic rashes behind the ears, on the eyelids, and other atypical areas.  Long-term effects include permanent joint damage and decreased range of motion and eye problems.
• Juvenile Vasculitis – variants include polyarteritis, Wegener’s granulomatosis, and Takayasu’s arteritis, but the most common symptoms include rash, arthritis, lung problems, abdominal pain, and renal dysfunction.  More serious cases can involve major organs, nerves, and the intestinal tract.  Some forms are more common in boys.
• Juvenile Scleroderma – thickening of the skin caused by increased collagen deposits that can lead to growth abnormalities, loss of skin elasticity, and Raynaud’s phenomenon.  Disease can be localized or systemic, affecting multiple organs, and affects more girls than boys.
• Juvenile Dermatomyositis (JDMS) – skin rash and weakened muscles caused by inflamed blood vessels in skin and muscle tissue.  Affects 3,000-5,000 children in the United States.
• Juvenile Spondyloarthropathy Syndromes – family of disorders characterized by arthritis in the spine, sacroiliac and other large joints, and eye inflammation.  Occurs more often in boys than girls. 

Rheumatic diseases can range from being very localized and mild to systemic and potentially life threatening.  Because of the complex nature of the trajectories of pediatric rheumatic disease, it is crucial that a child suspected of having one of these illnesses visit a pediatric rheumatologist early in the illness to either establish or confirm the diagnosis, and to continue to be monitored throughout the duration of the illness to ensure proper use of pharmacotherapies as well as adjunctive therapies.  The involvement of a pediatric rheumatologist also enhances access to novel therapies and therapies available only through clinical trials.  In addition, a child with a rheumatic disease may require the care of a team of physicians and other providers to ensure that all physical and emotional symptoms are being addressed.