Gross Appearance

The gross appearance of the joint fluid often yields important information. Normal synovial fluid is clear and colorless or straw colored. In the course of aspiration, blood vessels may be punctured, and sanguineous streaks may be found in the joint fluid. This uneven distribution of blood in the syringe is distinguishable from the appearance of the fluid aspirated in acute traumatic hemarthrosis, which is entirely sanguineous. In chronic hemarthrosis the fluid may be xanthochromatic. With inflammation the joint fluid becomes turbid. The greater the degree of inflammation, the more turbid the synovial effusion will be. The fluid from a pyogenic joint has the creamy or grayish appearance of frank pus. In rheumatoid arthritis the fluid may be clear in the early stages, but it becomes turbid as inflammation increases. The fluid in acute gout is milky white because of its urate content. In degenerative arthritis, the joint fluid is almost normal in appearance.

Viscosity and Mucin Clot

The concentration and quality of hyaluronate are altered in inflammatory states, with resultant changes in the physical characteristics of the synovial fluid. The fluid should be examined at the time of aspiration. The examiner notes its viscosity by “pulling” it between the gloved fingers and by letting it drop from a syringe. Normal fluid should form a string at least 1 inch long. Mucin quality can be tested by adding the fluid to either distilled water or 5% acetic acid. The clot that forms is graded as follows: normal; fair, characterized by some loss of clot continuity; poor, in which small, friable masses of clot are seen in a cloudy solution; and very poor, characterized by a few flecks in cloudy solution.

Microscopic Examination

Synovial fluid may be examined for cellular elements, intracellular inclusions, and crystals. Glucose and protein levels are also determined. Normal synovial fluid has fewer than 300 white blood cells (WBCs)/mm ³ , and the cell types may be determined. Normal fluid has less than 25% polymorphonuclear leukocytes. Specialized microscopy may reveal cytoplasmic inclusions of immunoglobulin, rheumatoid factor (RF), and complement components. Crystals may be seen with polarized light microscopy.

Other Examinations

It is important to determine glucose levels because the difference between serum and synovial fluid glucose levels increases with more severe inflammation. Septic arthritis lowers the joint fluid glucose level more than in other conditions, and this finding is of diagnostic importance. The normal protein content of synovial fluid is approximately 30% that of serum. The total protein level is usually 1.8 g/dL, 70% albumin, and 7% α ₂ -globulin. Normal values and common abnormalities are listed in Table 26-1 . With inflammation, the permeability of the synovium to plasma increases, and the protein content of the joint approaches that of serum. In addition, clotting factors enter the joint, and the inflammatory fluid forms clots.

Pauciarticular Juvenile Idiopathic Arthritis

Approximately half the cases of JIA in children are of the pauciarticular form, which by definition includes only cases with fewer than five joints involved. Girls affected by this variety of the illness outnumber affected boys by a ratio of 7 : 3. In other words, an affected child is twice as likely to be female than male. The peak period of onset is between 2 and 4 years of age, with half of affected children coming to medical attention before 4 years of age. Approximately 70% of children with pauciarticular JIA have a positive antinuclear antibody test result and will eventually develop iritis. The outlook for remission of pauciarticular JRA is approximately 34% to 54% over the 10-year period after diagnosis. Among patients with oligoarthritis and late onset of JCA, a lower probability exists for remission among those who are human leukocyte antigen–B27 (HLA-B27) positive.

Pauciarticular JIA manifests as a low-grade inflammation of one or several joints in an otherwise well child. In approximately half these patients only one joint is involved. The knee is most often affected, with the ankle–subtalar and elbow joints next in frequency ( Fig. 26-4 ). Hip involvement is unusual and, when present, may raise other diagnostic considerations. The small joints of the hands and feet are usually spared. Cervical spine involvement is extremely rare. On presentation, one or several joints may be involved. Over several months other joints may become inflamed, but in half the pauciarticular cases only one joint is involved.

Typical appearance of a young girl with a swollen knee of pauciarticular juvenile rheumatoid arthritis.

The clinician will make a correct diagnosis by taking a careful history and by performing a careful examination of all the joints, not just those of the chief complaint. A history of insidious onset without precipitating trauma is common, although occasionally some traumatic event calls attention to the joint. Morning stiffness is a frequent complaint, with symptoms decreasing during the day as the joint is used. The swelling is persistent; it may gradually increase but usually does not change dramatically from day to day. By convention, a duration of 6 weeks of arthritis is necessary for the diagnosis of JRA to be considered.

The involved joints are usually mildly tender and swollen. The swelling is a combination of synovial thickening and joint effusion. The degree of swelling is often out of proportion to the degree of tenderness or the amount of pain. The joint is warm but usually not erythematous, and the patient has some loss of range of motion and some pain when the joint is moved. The child will continue to bear weight. Joints that are red and exquisitely tender likely have a diagnosis other than JIA. The differential diagnosis includes oligoarticular-onset juvenile psoriatic arthritis (oligo-JPsA) and septic arthritis. Patterns of joint involvement may differentiate oligo-JPsA, in which small joint disease of the hands and feet is significantly more frequent in oligo-JPsA than in pauciarticular JRA. Patients with septic arthritis typically present with fever and an inability to bear weight, an erythrocyte sedimentation rate (ESR) of 40 mm/hr, and a WBC count greater than 12,000 cells/mm ³ , with larger joints most often involved. Ultrasonographic evaluation confirms the presence of excess fluid in the joints of patients with septic arthritis. Joint aspiration provides relief of symptoms and a specimen for culture, sensitivity, cell count, and differential to facilitate diagnosis. By comparison, a septic joint is exquisitely tender and the limitation of motion is much greater than in the inflamed joint in JRA.

Uveitis is a serious associated problem and may ultimately affect the child’s vision. It may be present at onset; in 20% of children it develops over the course of the disease. An early diagnosis can be made on finding increased protein levels and inflammatory cells in the anterior chamber of the eye on slit-lamp examination. Later, posterior synechiae form and tether the iris to the lens; the result is an irregular and poorly reactive pupil. Band keratopathy and cataracts occur late but eventually may involve 42% to 58% of patients with uveitis. Most cases are asymptomatic, and ophthalmologic examination is essential to allow early treatment.

The course of the disease is relatively benign. The arthritis waxes and wanes and is usually responsive to medical control. Over a period ranging from 3 to 11 years, the disease usually resolves. The average duration of disease is 2 years 9 months, and in half these cases it is less than 2 years. In approximately one third of cases progressive involvement of more joints occurs, so that the disorder resembles typical polyarthritis with somewhat fewer joints involved ( Box 26-1 ). Regarding indicators of long-term prognosis in JRA, male sex is correlated with increased disability in systemic-onset JRA, but with less disability among patients with RF-negative disease and with shorter active disease duration in patients with RF-positive polyarticular-onset JRA. The presence of antinuclear antibody correlates with longer active disease duration in patients with pauciarticular-onset JRA. Younger age at disease onset predicts longer active disease duration in patients with pauciarticular and RF-negative polyarticular JRA and shorter active disease duration in patients with systemic-onset JRA. Early disease onset and female sex are early indicators of unfavorable outcomes in JRA.

Polyarticular-Onset Juvenile Rheumatoid Arthritis

When five or more joints are involved within the first 6 months of illness, the syndrome is by definition polyarticular JRA. Two peaks of onset exist, the first between 1 and 3 years and the second between 8 and 10 years of age. Girls predominate in the later age group, which may in fact represent early-onset adult rheumatoid arthritis. The remission rate is estimated at 15% to 50% during the 10-year period after diagnosis. Polyarticular JRA has many characteristics in common with the pauciarticular form. The onset is insidious, the large joints of the lower extremity are often involved, the inflammation is chronic, and pain and swelling are moderate. The small joints of the hands and feet are commonly involved, as are the joints of the cervical spine and the temporomandibular joints ( Figs. 26-5 and 26-6 ). The affected joints are warm, tender, painful on motion, and swollen, with synovial thickening and effusion. Joint range of motion is almost always limited; this is initially caused by protective muscle spasm and later by destruction of articular cartilage and fibrosis. Affected children typically appear apprehensive and guard their painful limbs against movement. Symptoms arising in the temporomandibular joint are often described as “earache,” and symptoms arising from the sternoclavicular and costochondral joints are described as “chest pain.” On occasion, hoarseness and laryngeal stridor may result from inflammation of the cricoarytenoid joints. Cervical spine involvement with fusion of the apophyseal joints results in limitation of neck motion. Involvement of the temporomandibular joint causes failure of development of the lower jaw and results in a receding chin.

Swelling of the wrist and metatarsophalangeal and proximal interphalangeal joints of the hand in polyarticular juvenile rheumatoid arthritis.

Radiographic changes of juvenile rheumatoid arthritis of the wrist. Carpal destruction and volar subluxation are common findings.

Some systemic manifestations may be present and include low-grade fever, hepatosplenomegaly, lymph­adenopathy, and subclinical pleural and pericardial inflammation.

A major distinction is made between children with RF-positive polyarticular disease and those with RF-negative disease. RF-positive disease in children is in many ways similar to the adult form of rheumatoid arthritis. These children have rheumatoid nodules, erosion of joint surfaces, and a disease course that extends well into adulthood ( Fig. 26-7 ). Children with RF-negative disease have less involvement of the small joints of the hands and feet and do not form nodules.

Arthritis of the knees and ankles in a child with seropositive polyarticular juvenile rheumatoid arthritis.

Systemic-Onset Juvenile Rheumatoid Arthritis

The systemic form of JRA is a serious disease in which arthritis is only one manifestation of a generalized disorder. It affects 20% of children with JRA and is associated with the worst long-term prognosis; in many cases it results in severely damaged or destroyed joints. Remission occurs in approximately 29% to 50% of children within 10 years of diagnosis. Many organs and systems may be involved, including the liver, spleen, pleura, pericardium, and skin. Uveitis is rare. A febrile course with one or two daily spikes from normal to 39° C or 40° C is typical. The temperature spikes most often occur late in the afternoon, and the temperature rapidly returns to baseline. During the febrile periods these children are listless and appear ill but may seem well once they defervesce. The fever usually does not respond to salicylates or nonsteroidal agents.

Affected children usually have a characteristic rash with discrete, erythematous maculae 2 to 5 mm in diameter ( Fig. 26-8 ). The rash is classically a salmon color but may be more reddish in the early stage. It is located on the trunk, face, palms, soles, and proximal extremities and tends to migrate fairly rapidly. A clear halo is often visible around the maculae, and the larger maculae may be clear in the center.

Typical rash of systemic-onset juvenile rheumatoid arthritis.

Hepatosplenomegaly and generalized lymphadenopathy are often present. Enlarged, inflamed mesenteric lymph nodes may cause abdominal pain and distention, suggesting an acute surgical abdomen. The enlargement of abdominal organs usually resolves over a few months. Pericarditis and pleural effusions occur in approximately 10% of children with systemic disease and may manifest with nonspecific chest pain. Electrocardiographic changes are present, and the cardiac silhouette is enlarged on the chest radiograph. The cardiac manifestations are usually transient and rarely result in congestive heart failure. The presence of pericarditis is not related to the severity of the disease in general or to the joint manifestations.

Amyloidosis is a grave complication that is rare in North America, but in Great Britain it occurs in approximately 7.5% of cases. It manifests with proteinuria and hypertension. Immunoglobulin G and C-reactive protein (CRP) levels are elevated in patients who develop amyloidosis. Control of the activity of the inflammatory disease is the mainstay of prevention of amyloidosis.

Medical Treatment

The nonsteroidal antiinflammatory drugs (NSAIDs) are the mainstays of treatment of most patients. Although aspirin was the initial agent of choice, modern agents supply more potency with fewer side effects. Aspirin is given in a dosage of 75 to 90 mg/kg/day, usually in four divided doses with food, to seek a therapeutic salicylate level of 20 to 25 mg/dL. Ibuprofen is given in a dosage of 35 mg/kg/day, again in four doses with food. Naproxen is used at 15 to 20 mg/kg/day twice a day. Tolmetin sodium is given in a dosage of 25 to 30 mg/kg/day in three doses. At this time only these three NSAIDs are approved by the U.S. Food and Drug Administration for use in children.

In more severe disease not responsive to NSAIDs, other drugs that are more toxic may be efficacious, although approximately one third of all patients will not respond adequately to methotrexate. Low-dose methotrexate and other cytotoxic drugs may have a rapid effect on resistant disease. Methotrexate is given weekly either orally on an empty stomach or by subcutaneous administration, which is usually well tolerated, although it causes nausea and vomiting in some children and, rarely, hepatic toxicity. Hematologic, hepatic, and pulmonary monitoring is mandatory when these agents are used. A group of agents, the slow-acting antirheumatic drugs (or SARDs), includes antimalarial agents (hydroxychloroquine), parenterally administered gold compounds, and penicillamine. For patients who fail to respond to first-line drugs these drugs may be effective, but they are slow acting, requiring 3 to 6 months for full effect. If significant improvement does not occur within a few months of beginning methotrexate, then sulfasalazine, hydroxychloroquine, or other antirheumatic agents should be added. The tumor necrosis factor (TNF) inhibitor etanercept is also effective and well tolerated by patients with JRA. An intravenous form of the monoclonal anti-TNF agent infliximab is also available. Use of both these TNF-inhibiting agents is associated with increased infection risk resulting from reduced TNF action.

Intraarticular glucocorticoids are indicated and may be effective treatment for recalcitrant joint inflammation. These agents may be administered after joint lavage in refractory disease and typically bring significant clinical improvement within a few days. The average duration of response after each injection is 1 year, and early repeated injections (e.g., three injections over 42 months) may prevent leg length discrepancy by long-term inhibition of synovitis. Intraarticular injections reduce pannus formation and have no detectable deleterious effect on cartilage. Intraarticular injection of glucocorticoids can be performed successfully in children sedated with oral midazolam, although general anesthesia is advisable if several joints must be injected or if the hip or subtalar joint is to be treated. Triamcinolone hexacetonide is the preferred steroid for this purpose because of its long duration of action. Systemic steroids are indicated for life-threatening systemic disease but are not indicated in the long term because of the side effects of iatrogenic Cushing syndrome and irreversible growth impairment. Ophthalmic glucocorticoids are used to treat chronic uveitis.

Physical and Occupational Therapy

Physical and occupational therapists should be involved in the clinical team managing children with chronic arthritis. The goals of such therapy are to relieve pain, increase range of motion, improve muscular coordination, and help the patient relearn physiologic functional patterns. Therapists also help children learn about joint protection and self-care. Splinting on a selective basis is useful, and adapted footwear and walking aids may be used. Splinting of the wrists and hands may reduce the tendency toward joint contracture and subluxation. Occasionally, splinting of the knee or ankle at night is indicated to maintain range of motion.

Physical conditioning in children with arthritis is often poor, with decreased aerobic capacity and exercise tolerance in proportion to the severity of the disease. Disuse atrophy of muscles, joint contractures, and anemia contribute to deconditioning. Rehabilitation of children with arthritis should include conditioning training in addition to standard physical therapy activities. Conditioning requires that muscles be challenged with repetitive, progressive stress with exercises aimed at specific muscle groups. When joints are acutely inflamed, isometric exercises are recommended. Dynamic exercise can begin when the arthritis is in subacute or chronic stages. A general guideline is to have the child lift the maximum weight he or she can lift for 10 repetitions. That weight is then used for 2 or 3 sets of 2 to 10 repetitions for each muscle to be exercised. That weight is gradually increased. Low-impact sports such as walking, swimming, cycling, or low-impact aerobic dance are more appropriate than are highly competitive sports. Although excessive exercise may aggravate an inflamed joint, specific restrictions should be applied only when the management team is relatively certain of a deleterious effect.

Controlled studies of physical therapy interventions with standardized measurement techniques have not shown a positive long-term effect on the arthritic disease, nor have they shown a negative effect. One study reported that children with juvenile arthritis who receive massage therapy from their parents for 15 minutes a day for 30 days showed significant reduction in pain and anxiety and improved activity level compared with a control group of children who engaged in relaxation therapy.

Orthopaedic Treatment

Chronic joint inflammation results in a cycle beginning with muscle spasm to protect the painful joint from motion. If continued, the cycle leads to contracture of the muscle and joint capsule and disuse of the extremity, with resultant osteopenia. The orthopaedic management of JRA is concerned with interrupting this cycle. Thus management emphasizes maintenance of joint range of motion and extremity alignment and length, reduction of synovial proliferation, observation of cervical spine stability, and ultimately joint replacement as needed. Synovectomy remains a controversial modality. Releases about the hip and knee are sometimes needed; rarely, cervical spine instability requires treatment, and hand and foot deformities are sometimes correctable. All operative procedures in patients with JRA require careful preanesthetic evaluation. Cervical spine stiffness and instability, reduced mobility of the jaw with hypoplasia of the mandible, and coexisting medical conditions may require specialized approaches for intubation and recovery.

Synovectomy may be helpful for severely affected, recalcitrant joints but has not been shown to alter the long-term outcome of joint disease. * Although some studies showed that a new, relatively normal synovial lining regenerates after removal of inflamed synovial tissue, other studies reported frequent recurrence of disease. The results of synovectomy are best in large joints, and the knee is the most common joint so treated. Similarly, the best results with synovectomy are obtained if the procedure is performed early, before significant joint destruction has occurred. Successful synovectomy results in a reduction in swelling and pain. Range of motion is not improved after synovectomy, and care is necessary to avoid losing motion. Arthroscopic synovectomy is associated with less postoperative stiffness and morbidity, and postoperative continuous passive motion may be helpful. Synovectomy is indicated when a trial of medical management for more than 6 months (including intraarticular steroids) has failed.

* References .

Release of knee flexion contracture is best performed with the patient prone. Usually the hamstrings, lateral intermuscular septum, and iliotibial band are released. If necessary, one or both tendinous portions of the gastrocnemius muscles are sectioned and the posterior capsule of the knee is also released. Occasionally the anterior cruciate must be cut to correct posterior tibial subluxation. To avoid posterior subluxation, the postoperative cast must be molded to displace the tibia anteriorly as the knee is extended. If full correction cannot be obtained without neurovascular compromise, subsequent cast changes while the patient is under anesthesia may be required. Postoperative night splinting for up to 6 months is recommended to prevent recurrence.

Flexion contractures of the hip also respond to soft tissue releases. These procedures are indicated when a significant contracture that interferes with ambulation persists after 6 months or more of aggressive medical therapy. Swann and Ansell reported a reduction in flexion contractures after psoas and adductor tenotomy, with improvement still evident 3 years after surgical treatment.

Growth disturbances are most often seen at the knee. When a valgus deformity is present, either epiphyseal stapling or percutaneous partial epiphysiodesis will correct the deformity without major surgical trauma. The epiphysiodesis approach is preferred because of the minimal incision required. The procedure should be performed when growth prediction based on bone age shows 2 to 3 cm of growth remaining at the distal femoral epiphysis. Rydholm and colleagues reported that stapling of the distal femoral epiphysis for valgus was effective in correcting the deformity in 15 of 17 patients so treated. Stapling was also effective in correcting leg length inequality.

Scoliosis occasionally occurs in patients with JRA and may be managed by conventional means. Micrognathia secondary to temporomandibular involvement may be successfully treated by odontoidectomy through the transoral approach by using a sagittal split mandibular osteomy.

Total Joint Arthroplasty

Total joint arthroplasty is an appropriate and effective therapy for adolescents with polyarticular disease and painful, stiff, destroyed joints. Hip disease ultimately develops in 30% to 50% of all children with JRA, although more recent aggressive treatment approaches and more effective drug therapy have reduced the proportion of children in whom severe hip disease develops. Consequently the incidence of hip surgery has decreased, and outcomes of hip arthroplasty have improved. Hip and knee replacements have a well-established role in improving the function and well-being of the patient. Wrist, elbow, and ankle replacements may be useful, but there is less clinical experience with them.

Total hip or knee arthroplasty is indicated in the adolescent with marked functional impairment or severe disabling pain from advanced structural hip or knee joint involvement (see Fig. 26-9 ). Careful planning with a team approach is essential and should include consideration of high school and college education, use of crutches, medications, and emotional status. Preoperative planning includes procuring miniature or custom-made hip prostheses in up to half these patients. When both hip and knee replacements are necessary, it is best to approach the hip first because it is more difficult to rehabilitate the knee in the presence of a painful, contracted ipsilateral hip. In addition, it is useful at times to manipulate and cast the knee to gain extension at the time of the total hip arthroplasty.

Total hip replacement may be performed in a child with growth remaining. Knee replacement in the setting of open epiphyses is indicated if minimal growth remains. One series of knee replacements with open physes reported no growth disturbances, but all epiphyses had closed within 2 years of replacement.

Total joint replacements are difficult to perform in these patients as a result of osteopenia, contractures, and coexisting medical conditions. Cementless arthroplasties are gradually replacing cemented prostheses because of late loosening.

The results of hip and knee replacement are remarkable. Relief of pain is reported in almost all patients after hip replacement and in a high percentage after knee replacement. Improvement in range of motion is excellent at the hip and good at the knee. Most important, functional status improves in a high percentage of patients, often to a remarkable degree. Rates of loosening of hip components range from 12% at 4.5 years to 43% at more than 5 years after the surgical procedure. Prosthesis survival rates (still functioning) are up to 92% at 10 years and 83% at 15 years. ^†

† References .