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Juvenile Rheumatoid Arthritis

Introduction

Juvenile rheumatoid arthritis (JRA) is a condition of chronic synovitis in children of which there are several distinct subgroups (Table 1). The classic adult-type rheumatoid arthritis does occur in children but is quite rare, the JRA subgroups seronegative* polyarthritis and systemic-onset disease also occur in adults but not frequently, the pauciarthritis of early childhood has not been recognized in adults, and

Incidence and Epidemiology

The true incidence of JRA is not known. Based on the estimate that approximately 5% of all cases of chronic so-called "rheumatoid" arthritis begin during childhood, there would be about 250,000 children who have JRA in the

No causes or risk factors have been identified for JRA. Antecedent causes that frequently are mentioned include infectious agents, immunologic abnormalities of the host, physical trauma to joints, psychological trauma to the child, and allergy or

Pathophysiology

The synovial tissue, or lining tissue of the joint, is the target for inflammation in JRA. Early results of synovial inflammation include hypertrophy of

TABLE 1. Recognizable Subgroups Of JRA

% OF

SUBGROUP PATIENTS CHARACTERISTICS

Systemic-onset Disease 10% to 20% Systemic manifestations

Slight male preponderance

Seronegativity: RF* and

ANA*

Severe arthritis in 25%

Polyarticular Disease 20% to 30% Symmetric polyarthritis of

RF-negative polyarthritis small and large joints

Female preponderance

Early or late childhood

onset

ANA in 25%

Rheumatoid nodules

common

Severe arthritis in 10%

to 15%

RF-positive polyarthritis 5% to 10% Symmetric polyarthritis of small and large joints

Female preponderance

Late childhood onset

ANA in 50% to 75%

Rheumatoid nodules

common

Severe arthritis in >50%

Pauciarticular Disease 30% to 40% Arthritis of few joints

Early childhood-onset Hips/sacroiliac joints spared

Female preponderance

Early childhood onset

ANA in 60%, RF-negative

Chronic iridocyclitis in 30%

Mild arthritis

Late childhood-onset 10% to 15% Arthritis of few joints Hips/sacroiliacs often

affected

Male preponderance

Late childhood onset

ANA-negative, RF-negative

HLA-B27 in 75%

Some will have spondyloarthropathy as adults

*RF = rheumatoid factor; ANA = antinuclear antibodies.

The etiologic agent or agents for the synovitis in JRA are unknown. The synovitis is characterized by its chronicity. Immunologic mechanisms such as immune complex disease may perpetuate the synovitis, but full explanations for the chronicity of synovial inflammation remain to be found. If synovitis persists long enough in an individual joint, structures of the joint may be damaged. Because articular cartilage does not regenerate well, this destruction may be permanent. Fortunately, many children who

TABLE 2. Names Currently Used To Describe Condition(s) of Chronic Synovitis in Children

$ Juvenile rheumatoid arthritis

$ Juvenile chronic polyarthritis

$ Juvenile chronic arthritis

$ Still disease

$ Chronic childhood arthritis

JRA may involve other organ systems in addition to the joints, and patterns of organ involvement differ in various subgroups. Possible extraarticular manifestations include the iridocyclitis of early childhood pauciarticular disease; the rheumatoid nodules and rheumatoid vasculitis of seropositive disease; the fevers, rash, polyserositis, hepatosplenomegaly, lymphadenopathy, anemia, leukocytosis, and (rarely)

Clinical Manifestations

The clinical manifestations of JRA are diverse. Although a number of clinically distinct subgroups of disease have been suggested, there is no complete agreement as to which subgroups are valid. The American Rheumatism Association currently recognizes three subgroups: systemic-onset disease, polyarticular-onset disease, and

TABLE 3. Objective Signs of Arthritis

Joint Swelling

--Synovial hypertrophy

--Increased amounts of synovial fluid

--Swelling of periarticular tissues

Joint Pain

--On motion

--On palpation (tenderness)

--At rest

Loss of Joint Motion

--Stiffness of joints

Joint Warmth

Joint Erythema

Clinical Features

SYSTEMIC-ONSET JRA Systemic-onset JRA, characterized by high intermittent fevers and other extraarticular manifestations (Table 4), affects about 10% to 20% of all patients who have JRA. There is a slight male preponderance. The disease may present at any age during childhood and occasionally presents during adulthood.

The characteristic fevers of systemic-onset JRA are high and intermittent, with elevations to 39.5EC (103EF) or higher once or twice daily and subsequent returns to normal or

*Necessary for diagnosis

Prominent musculoskeletal involvement usually is manifest early in disease, although this may be overlooked in the face of the systemic illness. Nearly all children have severe myalgia, arthralgia, or transient arthritis during periods of temperature elevation; such transient musculoskeletal complaints may

POLYARTICULAR JRA

Polyarticular disease without the prominent systemic manifestations of systemic-onset JRA affects about 35% of children who have chronic arthritis. Two subgroups

Seronegative JRA

This subgroup of disease is heralded by the insidious or sudden onset of polyarthritis, often in early childhood. The high fevers and rash of systemic-onset

Seropositive JRA

This type of disease also is heralded by the sudden or insidious onset of arthritis, usually in many joints. Patients typically are older than 8 years at onset. Subcutaneous rheumatoid nodules often are found over pressure points, notably the elbows, the heels, the first metatarsophalangeal joints, and the knuckles and

PAUCIARTICULAR ARTHRITIS

Pauciarticular arthritis, or arthritis limited to only a few joints (Latin: pauci-few, articulus-joint), affects 40% to 50% of children who have JRA. This subgroup designation implies that arthritis remains limited to a few joints for the first

Early Childhood-onset

This subgroup, associated with chronic iridocyclitis and ANAs, appears to include 30% to 40% of all patients who have JRA. Girls are affected predominantly, and the

Later Childhood-onset

Pauciarticular disease associated with sacroiliitis and HLA B27 affects 10% to 15% of children who have so-called JRA. Males are affected predominantly, and the

Diagnosis

Diagnosis of JRA rests on several bases (Table 5): onset of disease during

Laboratory Studies

There are no specific or diagnostic laboratory tests for JRA. Acute phase reactants such as the erythrocyte sedimentation rate and C-reactive protein generally are elevated and present during periods of inflammation, but none of these tests is

Therapy

A number of considerations are important in designing therapy for children who have JRA. These include identification of the particular disease manifestations

ANTI-INFLAMMATORY AND ANTIRHEUMATIC AGENTS

When planning therapy for the arthritic and musculoskeletal manifestations of JRA, the physician initially should determine the extent of joint involvement, the activity of the synovitis, the amount of joint destruction, the status of muscle strength,

Nonsteroidal anti-inflammatory drugs (NSAIDs) remain front-line and important agents in the treatment of JRA. NSAIDs available for use in children in the United States include salicylates, naproxen, tolmetin, ibuprofen, and indomethacin; a number of other agents are used in adult medicine but are not yet approved for use in

Methotrexate has been shown to be an effective agent in many children who have severe JRA, and it is moving to the fore in the therapy of children whose disease is

"Disease-modifying" therapies that are being tried in therapy of JRA include sulfasalazine, intravenous immunoglobulin, corticosteroid therapy in various forms, and cyclosporin. Sulfasalazine is being used rather widely. Although

SURGERY

Orthopedic surgery can play a role in therapy of JRA. Synovectomy, the removal of inflamed synovial tissue, is of very limited usefulness in early therapy, but orthopedic surgery has great promise in the rehabilitation of children who have severe JRA. Leg length inequality, which may result from asymmetric arthritis affecting the knees

THERAPY OF SYSTEMIC MANIFESTATIONS

The systemic manifestations of systemic-onset JRA often respond to nonsteroidal therapy. Prolonged debilitating fevers and malaise, pericarditis or myocarditis with threat of cardiac decompensation, or severe anemia may be causes for