Discussion: INTRODUCTION
JRA is a group of diseases, of currently unknown etiology, characterized by chronic synovial inflammation and joint destruction. Cytokines released by leukocytes leads to synovial cell proliferation and production of angiogenetic factors that allow growth of a soft-tissue pannus that destroys the joint. In some patients the cytokines IL-6 and TNF are predominant.
EPIDEMIOLOGY
In the United States, approximately 10-20 people per 100,000 children have JRA.
Patients may be seronegative or seropositive for RF; the seronegative form is also sometimes called Still's disease. Between 5 and 15 percent of pediatric patients are seropositive; this is more common in females and in ages less than 10, and often results in rapid destruction. JRA is subtyped into mono/pauciarticular (40-55% of patients, one third of whom may have late-childhood onset); polyarticular (20-30%); and systemic (10-20%).
Polyarticular and early-onset pauciarticular forms are more common in girls, and there is a slight male predominance in late-onset pauciarticular and systemic-onset disease. Systemic-onset disease can occur in early childhood or later. Polyarticular JRA can occur throughout childhood and adolescence.
No particular racial difference in prevalence has been found, but African patients have been reported to be older and less likely to be ANA-positive or have uveitis, but have a higher incidence of IgM-RF positivity.
HISTORY AND PHYSICAL
JRA requires physical findings of arthritis or synovitis in at least one joint lasting at least 6 weeks with other causes excluded, with onset before 16 years of age.
Onset may be either acute or chronic. There may be morning stiffness, daytime joint pain, limping, weight loss with or without diarrhea, anorexia, or other systemic complaints. Pain and disability may lead to school absences or psychologic stress. Severe arthritis is not uncommon in most forms of the disease, with the exception of early-onset pauciarticular disease.
Symptoms may vary with the disease subset:
* Patients with systemic-onset JRA typically have spiking fevers that occur several times a day, and may have an associated temporary pink linear rash, usually on the trunk and extremities. Arthralgia is often present for several months (up to years) without findings of arthritis. Often hepatosplenomegaly and sometimes lymphadenopathy are present. Muscle tenderness or serositis may be present.
* Pauciarticular JRA affects 4 or fewer joints, typically the large weight-bearing joints. In early-childhood onset pauciarticular JRA, the hips and SI joints are typically spared, whereas in late-onset disease these are often affected. Involvement of the small joints of the hand is unusual and often predicts development of polyarticular JRA or psoriasis. Extensor muscle atrophy and knee and wrist flexion contractures are sometimes present.
* Polyarticular disease affects at least 5 joints, which may be large or small, and often has symmetric distribution.
DIFFERENTIAL DIAGNOSIS
Numerous other diseases can cause arthralgia or even arthritis. The long differential diagnosis includes:
Infections: septic arthritis; post-infectious or reactive arthritis.
Malignancies: ALL and neuroblastoma.
Autoimmune disorders: autoimmune hepatitis; AS; dermatomyositis,; scleroderma,; vasculitides; and lupus; vasculitides; inflammatory bowel disease.
Noninflammatory causes: trauma; AVN; orthopedic conditions (SCFA, LCPD, Osgood-Schlatter disease, etc.) and many others.
LABORATORY FINDINGS
Laboratory findings are nonspecific but can help to diagnose JRA.
ESR is always elevated, and fibrinogen and D-dimer are often positive.
ANA is positive in up to 25% of patients, especially in the early-onset pauciarticular form.
RF is rare in systemic JRA, but may mark patients at risk for persistence into adulthood.
Late-childhood onset pauciarticular disease is associated with HLA-B27 positivity in 3/4 of cases.
CBC may reveal lymphopenia or microcytic anemia; neutropenia or thrombocytopenia should suggest alternative diagnoses (ALL or SLE, respectively).
Liver function tests may reveal decreased total protein and album but ALT should be normal.
Urinalysis should exclude infection or nephritis.
IMAGING FINDINGS
Radiography is insensitive to early changes of JRA, but radiography of the affected joints should be performed to document any inflammatory arthritis and exclude other causes of arthritis such as infection. Hand findings include periarticular swelling early in disease; later findings include periarticular osteopenia around the MCP and IP joints; accelerated skeletal maturation; and carpal, radial, and ulnar erosive changes that may lead to ankylosis, as in this case. Leg findings include periarticular osteopenia; overgrowth of the knee epiphyses; epiphyseal erosions with decreased joint space; and expansion of the intercoldylar notch. The spine is involved in up to 70% of patients: the articular facets are affected most, and the discs are not at all affected; diffuse zygapophyseal ankylosis without disc abnormalities is diagnostic of JRA.
CT can exclude osteoid osteoma, and will show the radiographic findings.
Bone scanning may also be used to exclude infection if there is no physical finding of arthritis.
MRI can exclude trauma. Early findings include synovial hypertrophy and joint effusions, and, uncommonly, radiographically inapparent cartilage erosions. Evaluation should include contrast-enhanced imaging to demonstrate synovial enhancement.
MORBIDITY AND MORTALITY
Mortality is very low (less than 1%), but is increased in patients who progress to other forms of rheumatologic disease. Morbidity depends on the particular manifestation; psychologic morbidity associated with decreased quality of life can occur in all types but is more severe in polyarticular disease.
Systemic JRA patients can develop pericarditis, hemolytic anemia, DIC, endarteritis (which may lead to autoamputation of the digits), andmacrophage activation syndrome (in which RBC, PLT, and WBC all decline, and massive amounts of cytokines causes hypotension and hepatosplenomegaly).
Pauciarticular JRA can cause knee flexion contractures, uveitis (typically asymptomatic, and in young ANA-positive girls), and leg length discrepancy (asymmetric knee growth plate involvement).
Polyarticular JRA can lead to increased size of epiphyses, accelerated bone age, narrowed joint spaces, swan-neck or boutonniere deformities, and subluxations. The cervical spine may be involved, raising risk for subluxation.
TREATMENT
Treatment may consist of NSAIDS (usually good enough for pauciarticular disease) or other anti-inflammatory drugs like etanercept (Remicade). Some children may require intra-articular, oral, or IV steroids. Surgical options include joint replacement, but this should be delayed until after growth is complete.
