Kemedy K. McQuillen
Victoria S. Gregg
• NSAIDs, glucocorticoids, immunosuppressants, and biologic agents are treatment options for systemic lupus erythematosus (SLE) directed at ameliorating the underlying inflammatory process.
• Patients with suspected acute rheumatic fever (ARF) are admitted to the hospital. Penicillin is indicated to eradicate any residual carriage of group A β-hemolytic Streptococcus (GAβHS).
• Enthesitis-related arthritis is a rheumatic disorder that can present in later childhood or adolescence. It is characterized by involvement of the sacroiliac joints and lumbar spine, but patients may also have peripheral arthritis.
• Reactive arthritis is treated with anti-inflammatory agents: the role of antibiotic treatment is unclear unless Chlamydia trachomatis is the inciting infection.
• In juvenile idiopathic arthritis (JIA), polyarticular disease involves more than four joints and rheumatoid factor may be present or absent. Pauciarticular JIA involves four or fewer joints (most commonly leg joints but rarely hip involvement). Intermittent spiking fever may be the initial manifestation of systemic onset JIA.
Transient synovitis, also known as toxic synovitis, is the most common cause of hip pain in childhood. It is a self-limited condition caused by a nonpyogenic inflammatory response of the synovium. Its peak incidence is between 3 and 6 years of age and affects boys more commonly than girls with a slight predilection for the right hip. Less than 5% of cases are bilateral. Pain may be referred to the medial aspect of the thigh or knee. An association with active or recent infection, trauma, or allergic hypersensitivity is suspected. At least half the children with transient synovitis have or recently have had an upper respiratory illness.1
Affected patients either refuse to walk or walk with a limp. The leg is held in flexion with slight abduction and external rotation. Passive movement is usually pain-free; however, there may be pain and a slightly decreased range of motion with extreme internal rotation or abduction. Low-grade fever and malaise may be present. The diagnosis of transient synovitis is one of exclusion as laboratory values may be normal or may reveal mild elevations in the white blood cell (WBC) count and erythrocyte sedimentation rate (ESR). Clinical decision rules have been developed to help differentiate transient synovitis from septic arthritis based on the presence or absence of fever, the ability to bear weight, WBC counts, inflammatory markers (ESR and C-reactive protein [CRP]), side-to-side differences in the width of the joint space on radiographs, and prior visits to a health care provider (Chapter 108 and Chapter 61). In the absence of fever and without elevated WBC and ESR, septic joint is unlikely, and the diagnosis of transient synovitis can be made without obtaining joint fluid. AP and “frog-leg” lateral radiographs of the pelvis tend to be normal in transient synovitis; findings consistent with transient synovitis include medial joint space widening, an accentuated pericapsular shadow, and Waldenström’s sign, which is lateral displacement of the femoral epiphysis with surface flattening secondary to effusion. However, these findings are also apparent in Legg–Calvé–Perthes (LCP) disease and, if present, mandate close follow-up or further investigation with MRI. Although effusions are present in 60% to 70% of cases of transient synovitis, they are also present in septic arthritis, osteomyelitis, acute slipped capital femoral epiphysis (SCFE), LCP disease, rheumatoid and infectious arthritis, malignancy, and osteoid osteoma, thereby limiting the utility of an effusion on ultrasonography in determining the etiology of hip pain.2
Treatment involves rest via nonweight bearing or, in cases of extreme pain, bed rest and reduction of synovitis with anti-inflammatory medications.1 Children are allowed a gradual return to activity as the pain subsides and full, unrestricted activity is permitted when the hip is completely pain-free and the limp has resolved. Repeat examination is recommended for all children within 12 to 24 hours and again after 10 to 14 days if the symptoms have not resolved. Up to 75% of patients have complete resolution of pain within 2 weeks and 88% within 4 weeks. The remainder may have less intense, but persistent pain for up to 8 weeks. Relapse is infrequent, and usually occurs within 6 months.
SYSTEMIC LUPUS ERYTHEMATOSUS
SLE is a chronic but often episodic multisystem autoimmune disease with protean manifestations. Fifteen to twenty percent of cases of SLE are diagnosed in childhood with a median age of 12.2 years.3 SLE is rare in those younger than 5 years.4 The time from symptom onset to diagnosis ranges from 1 month to 3.3 years with a median of 4 months.3 Female patients are preferentially affected with a female:male ratio of 3:1 prepuberty and 9:1 after puberty. Native Americans, Hispanics, Chinese, and Filipinos are more susceptible to developing SLE and greater disease severity is seen in African Americans and Hispanics. Patients with lupus are more likely to have a relative with either lupus or another autoimmune disease such as thyroiditis or insulin-dependent diabetes.
The most common presenting findings of pediatric SLE (pSLE) include hematologic (anemia, lymphopenia, leukopenia, and/or thrombocytopenia), mucocutaneous (malar rash and/or oral ulcers (Fig. 110-1), musculoskeletal (arthritis or arthralgia), fever, and renal abnormalities. Sun exposure can exacerbate the skin disease and cause a systemic flare.
FIGURE 110-1. The characteristic malar rash of systemic lupus erythematosus. Note the extension across the cheeks and the nasal bridge with sparing of the nasolabial folds.
Most patients will have musculoskeletal involvement such as arthritis, arthralgia, myalgia, diffuse muscle weakness, tenosynovitis, periostitis, and, less commonly, myositis. The arthritis of pSLE tends to be nonerosive and nondeforming. It is painful, symmetric, and polyarticular and can affect small or large joints; prolonged morning stiffness is also common. Approximately 10% of patients with pSLE also develop avascular necrosis due to the illness or as a consequence of steroid therapy, most commonly affecting the hips and knees. Lupus and steroid therapy may also cause osteoporosis and vertebral fractures.
Approximately 75% of children with pSLE will have renal involvement, usually within 2 years of disease onset. Renal disease is the leading cause of serious morbidity and mortality in SLE. Early findings include microscopic hematuria and proteinuria; however, hypertension, decreased glomerular filtration rate, azotemia, and renal failure may develop. Lupus nephritis classification is based on histopathology and can range from normal by light microscopy (class I) to advanced sclerotic nephritis (class VI). As treatment differs for differing forms of SLE nephritis, renal biopsy is warranted. Renal flares are common and can frequently be detected by increasing proteinuria before constitutional symptoms develop (fever, malaise, anorexia, and weight loss).
Central nervous system (CNS) disease is the second leading cause of serious morbidity and mortality in SLE and is difficult to diagnose because of vague and varied complaints. Headache is the most common neuropsychiatric manifestation. Severe unremitting headache may reflect vasculitis, cerebral vein thrombosis (CVT), CNS infection, pseudotumor cerebri or organic brain syndrome. CVT may present without other CNS manifestations and is almost always associated with the presence of lupus anticoagulant. Other neuropsychiatric manifestations of pSLE include psychosis, altered mental status, cognitive dysfunction, cerebrovascular disease, seizures, movement disorders, neuropathy, and transverse myelitis.
Hematologic abnormalities include anemia, which may be from hemolysis, but most commonly reflects the presence of chronic disease. Thrombocytopenia can occur, as can leukopenia. Involvement of serosal membranes, including the pleura, peritoneum, and pericardium, is a prominent aspect of SLE and leads to complications that include pleuritis with or without pleural effusion, peritonitis, and pericarditis. Pericarditis can occasionally result in a clinically significant pericardial effusion. Cardiac complications include myocarditis, endocarditis, and premature atherosclerosis causing coronary artery disease. Pulmonary disease includes pneumonitis and, infrequently, pulmonary hemorrhage or pulmonary hypertension. Shrinking lung syndrome may also occur and results from diaphragmatic dysfunction that elevates the lung, resulting in decreased lung volume. Gastrointestinal (GI) disease is uncommon in pSLE but may include pancreatitis, mesenteric vasculitis, and hepatitis.
Although it is unlikely that the initial diagnosis will be made in the ED, it is important to exclude malignancies, especially leukemia, ARF, JIA, and infectious processes. Drug-induced lupus is seen in children as well as adults. The medications most commonly implicated are anticonvulsants (phenytoin and carbamazepine), isoniazid, and minocycline.5 If a patient with SLE symptoms is taking these medications, they should be stopped immediately.
In all patients with suspected SLE, a complete blood count, prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), serum electrolytes, blood urea nitrogen, creatinine, ESR, and CRP are indicated. Urinalysis will often reveal microscopic hematuria and proteinuria. If there is evidence of coagulopathy, lupus anticoagulant and antiphospholipid antibody tests are indicated. Antinuclear antibody (ANA), other autoantibodies, rheumatoid factor, complement studies, and quantitative immunoglobulins should be obtained. ANA is positive in almost all patients who have active disease but is not specific (may be positive in up to 33% of healthy patients). Antibodies to double-stranded DNA (anti-ds DNA) are more specific to SLE and are found in 60% to 70% of patients with SLE.3
Over the course of the illness, children with SLE develop malar rash, neurologic features (headache, chorea, seizures), and renal disease more frequently than do adults. Hematologic and renal involvement tends to be worse in children. Over the past several years, the overall prognosis of pSLE has improved due to earlier diagnosis and improved treatments; 92% 5-year survival rate and an 85% 10-year survival rate.4,6 The primary causes of death are renal disease, infection, and CNS disease.
Treatment of SLE includes NSAIDs, steroids, immunosuppressants, and biologic agents; the choice of medication depends on the extent of organ system involvement.
ARF is an autoimmune systemic inflammatory response to infection with GAβHS. ARF occurs after GAβHS pharyngitis but is not associated with streptoccocal infections of the skin. In developing areas of the world, the incidence of ARF exceeds 50 per 100,000 children with rates as high as 350 per 100,000 children in aboriginal children of northern Australia.7 Worldwide, rheumatic heart disease (RHD), a complication of ARF, is the most common form of acquired heart disease in all age groups and accounts for up to 50% of all cases of cardiovascular disease in many developing countries.8 In the United States, the rate of ARF is less than 10 per 100,000 children. Beginning in the mid-1980s there have been outbreaks of ARF in Salt Lake City, Ohio, western Pennsylvania, Tennessee, New York City, Missouri, and Texas, as well among military recruits in San Diego and at the Fort Leonard Wood Training base in Missouri.8
The incidence of ARF peaks between 5 and 15 years of age.8 Only 5% of episodes arise in children younger than 5 years and is almost unheard of in children younger than 2 years.7 ARF is more common in girls. It is most common during the winter and spring. Although ARF generally develops 2 to 4 weeks following the inciting infection, it may present weeks to months later. One-third of children do not recall an antecedent sore throat.
The main clinical features of ARF are outlined in the modified Jones Criteria (Table 110-1).9 The World Health Organization (WHO) has also developed criteria to aid in diagnosing ARF (Table 110-2). The WHO criteria are less stringent than the revised Jones criteria to reflect the increased incidence of ARF in developing countries. As diagnostic guidelines, they can be adapted to populations at high risk for ARF to improve the sensitivity for disease detection. Chorea and indolent carditis are not diagnosed until months after the onset of ARF and, due to waning or nonexistent antibody titers, do not require evidence of an antecedent GAβHS infection.
Diagnosis of Rheumatic Fever (Revised Jones Criteria)a,b
Diagnosis of Rheumatic Fever (WHO Criteria)a
Joint complaints are common in ARF and range from arthralgias to frank arthritis. Arthralgia is a minor manifestation of ARF in the absence of arthritis as a major criterion. The arthralgias are especially intense at night and can wake children from sleep. Pain is out of proportion to the clinical findings. Arthritis is a major manifestation of ARF and occurs in approximately 75% of cases. Classically, it involves larger joints, especially the knees, ankles, wrists, and elbows and is migratory. Monoarticular arthritis is less common but may occur, especially with early use of anti-inflammatory medications. Synovial fluid in ARF usually has 10,000 to 100,000 WBC/mm3 with a predominance of neutrophils, protein of ≥4 g/dL, normal glucose, and the ability to form a good mucin clot.8 ARF arthritis responds dramatically to salicylates. There tends to be an inverse relationship between the severity of the arthritis and the severity of carditis. Joint symptoms of ARF tend to resolve within a month and leave no permanent damage.
Patients with arthritis that is not typical of ARF but who have recently had a streptococcal infection may have poststreptococcal reactive arthritis (PSRA), which typically develops 3 to 14 days after the pharyngitis. It is nonmigratory and can affect small and large joints as well as the axial skeleton. It responds poorly to anti-inflammatory treatment and is unaffected by antimicrobial therapy. PSRA may last from 1 week to 8 months with a mean duration of 2 months.10 Laboratory evaluation of patients with PSRA shows a normal WBC count with an elevated ESR. Throat culture or rapid antigen test for GAβHS may be positive. Antibodies suggestive of a recent streptococcal infection may or may not be present but should manifest 3 to 4 weeks after initial evaluation. Approximately 5% of patients with PSRA develop carditis, and echocardiography is recommended at presentation and 1 year later. Because of the risk of carditis, patients with PSRA should receive antimicrobial prophylaxis with penicillin or erythromycin, to prevent recurrent streptococcal infection, for 1 year if carditis is not detected and for a minimum of 5 years if carditis develops.10
Carditis occurs in 50% to 60% of cases of ARF. Rheumatic carditis is characterized by pancarditis, with inflammation of the peri-, myo- and endocardium. Endocarditis (valvulitis) is universal whereas the presence of myocarditis and pericarditis is variable. Carditis and the resultant RHD account for most of the morbidity and mortality associated with ARF. The carditis can be clinically silent or severe enough to result in congestive heart failure. Acute rheumatic carditis usually presents with tachycardia and a cardiac murmur related to valvulitis (most commonly involving the mitral valve with or without the aortic valve). Valvular insufficiency is characteristic of acute and convalescent stages of ARF with valvular stenosis appearing years to decades after the acute illness. Echocardiographic findings in acute ARF may include pericardial effusion, decreased ventricular contractility, or mitral and/or aortic regurgitation. Echocardiographic demonstration of valvular insufficiency without auscultatory corroboration does not satisfy the Jones criteria for carditis. Patients with valvulitis are at risk for developing infective endocarditis.
Sydenham chorea, which is due to an autoimmune insult to the basal ganglia,11 occurs in 10% to 15% of patients and may be the only manifestation of ARF; involuntary choreiform movements and facial grimacing are exacerbated by stress and disappear with sleep. Mild cases may present with restlessness and clumsiness. The motor movements may be unilateral. Symptoms are often preceded by behavioral disturbances including emotional lability, personality changes, anxiety, and poor school performance. Some patients may have “Sydenham speech” that is characterized by bursts of dysarthric speech. The time to development of chorea (1–6 months) is longer than for arthritis or carditis, and because of the insidious onset of symptoms and delays in diagnosis, streptococcal antibodies may be decreasing or undetectable at presentation. Physical findings of chorea include irregular contractions of the hands when squeezing the examiner’s finger (milkmaid’s grip), spooning and pronation of the hands when the arms are extended, and wormian movements of the tongue upon protrusion. Alterations in handwriting may be noted. The duration of chorea varies, but it is a self-limited process. Recurrence has been reported in 20% to 60% of patients and usually occurs within 2 years of initial presentation.11 Sixty-three to ninety-four percent of patients with Sydenham chorea will also have cardiac involvement.11
The dermatologic manifestations of ARF are infrequent. Erythema marginatum is a nonpruritic, erythematous, serpiginous macule with a pale center occurring on the trunk and extremities and typically sparing the face (Fig. 110-2). It is accentuated by warming the skin.8 Subcutaneous nodules are firm, painless, and located along the extensor surface of the tendons near bony prominences. They are approximately 1 cm in diameter.
FIGURE 110-2. Erythema marginatum: one of the major manifestations of acute rheumatic fever.
The differential diagnosis of ARF is extensive. ARF arthritis may mimic findings associated with septic arthritis, JIA, reactive arthritis, serum sickness, malignancies, SLE, Lyme disease, and sickle cell disease.
Diagnostic evaluation for ARF includes throat culture and rapid antigen testing for GAβHS, titers for antistreptolysin O, anti-DNase B, antihyaluronidase, ESR, and CRP. An EKG and echocardiogram are indicated. A chest radiograph can exclude congestive heart failure.
Patients with suspected ARF are admitted to the hospital. Ten days of orally administered penicillin or erythromycin or a single intramuscular injection of benzathine penicillin is indicated to eradicate GAβHS infection. Patients with arthritis but without carditis are managed with high-dose aspirin (100 mg/kg/d in four divided doses). Consideration should be given to withholding anti-inflammatories if arthralgia or atypical arthritis is the only manifestation of presumed ARF while the patient is observed for more definitive findings. Patients with carditis and cardiomegaly or congestive heart failure are treated with prednisone (2 mg/kg/d in four divided doses). Digoxin, fluid and salt restriction, diuretics, and oxygen may also be beneficial. Chorea may respond to haloperidol, Thorazine, valproic acid, or carbamazepine.
Patients with ARF are vulnerable to recurrent attacks that may cause or exacerbate valvular damage. Recurrent attacks can be prevented by prophylactic administration of antibiotics. First attacks can be prevented by prompt treatment of streptococcal pharyngitis.
Spondyloarthropathies include enthesitis-related arthritis (formerly known as juvenile ankylosing spondylitis), psoriatic arthritis, inflammatory bowel disease-related arthritis, and reactive arthritis. The typical characteristics of each entity are outlined in Table 110-3. The spondyloarthropathies are characterized by inflammation of joints of the axial skeleton and limbs, the presence of enthesitis, and by the absence of rheumatoid factor. Tenosynovitis and periostitis may also occur. Enthesitis is characterized by chronic inflammation at the sites of tendon, ligament, fascia, and capsule attachment to bone. Tenderness from enthesitis may be noted in the chest wall, iliac crest, ischial tuberosity, posterior or plantar surface of the heel, metatarsophalangeal area, and anterior tibial tuberosity. The inflammatory changes result in calcification of ligaments and fusion of joints in adulthood.
Characteristics of Spondyloarthropathies
ENTHESITIS-RELATED ARTHRITIS (JUVENILE ANKYLOSING SPONDYLITIS)
Although enthesitis-related arthritis in children tends to have a greater frequency of extra-axial symptoms than in adults, it is still considered to belong to the group of spondyloarthropathies. Involved joints may include the spine (Fig. 110-3), sacroiliac joints, and lower extremities, including the hips. During the first 6 months of disease, hip joint arthritis may be the only finding. Patients often complain of hip, back, and thigh pain that is worse at night and improves with movement. Upper-extremity involvement is uncommon and more suggestive of another type of JIA. Systemic symptoms include fatigue and low-grade fever. Enthesitis at characteristic locations around the foot and knee is common and is part of seronegative enthesitis and arthritis (SEA) syndrome with seronegativity referring to the absence of rheumatoid factor. SEA is probably the most common initial presentation of enthesitis-related arthritis.12 Physical examination of patients with enthesitis-related arthritis may reveal tenderness over the sacroiliac joints and loss of range of motion of the lumbar spine. Radiographic evidence of sacroiliitis is absent until late in the disease. MRI is able to identify sacroiliitis much earlier. Acute, painful iridocyclitis occurs in up to 25% of patients with enthesitis-related arthritis. Less commonly, patients may have low-grade fever, aortic valve insufficiency, aortitis, muscle weakness, or atlantoaxial subluxation. Long periods of active disease interspersed with long periods of remission characterize the disease. Over the long term, the enthesitis-related arthritis may cause fusion of the spine and SI joints with disability.
FIGURE 110-3. Radiograph of patient with enthesitis-related arthritis. Note the narrowed joint spaces between C6/C7 and C7/T1 with ankylosing of C6 to T1 vertebral bodies.
Although psoriatic arthritis is most commonly an asymmetric oligoarthritis that affects the knees, ankles, and small joints of the hands and feet, it may present with symmetric distal interphalangeal joint disease or HLA-B27-associated sacroiliitis. Psoriatic rash, nail pitting, dactylitis, onycholysis, or a family history of psoriasis supports the diagnosis. Chronic iridocyclitis occurs in 10% to 15% of children with psoriatic arthritis. Up to 50% of affected patients have ANAs present. Psoriatic arthritis tends to be a chronic unremitting disease.
INFLAMMATORY BOWEL DISEASE–RELATED ARTHROPATHIES
Ulcerative colitis and Crohn disease may be complicated by two types of arthritis: a peripheral polyarthritis that is not a true spondyloarthropathy and is reflective of GI inflammation or, less commonly, an HLA-B27- associated spondyloarthropathy of the sacroiliac and peripheral joints that is independent of GI inflammation. Associated findings may include erythema nodosum, pyoderma gangrenosum, fever, weight loss, and anorexia. Although the peripheral arthritis of inflammatory bowel disease is usually controlled when the GI symptoms are controlled, the HLA-B27-associated arthritis tends to be more chronic.
A GI infection with Salmonella, Yersinia, Campylobacter, or Shigella, a GU infection with C. trachomatis or infection with Mycoplasma pneumoniae or Chlamydia pneumoniae usually precedes the reactive arthritis.13,14 Although it is considered a sterile synovitis, bacterial degradation products and bacterial DNA have been isolated in affected joints. Reactive arthritis is usually oligoarticular and may be associated with considerable pain, swelling, and erythema with symptoms starting 1 to 4 weeks after the inciting infection.13 (Associated findings in Table 110-4.)13,14 Approximately half of affected patients have symptom resolution within 6 months while the rest develop a chronic reactive arthritis that may exhibit a relapsing course.13 Enthesitis may be prominent. HLA-B27 positive patients may develop sacroiliitis. Mild chronic diarrhea may develop after post enteric reactive arthritis.13
Findings Associated with Reactive Arthritis13,14
The diagnosis of spondyloarthropathy is based on historical and clinical features; laboratory evaluations are helpful in excluding other etiologies. Laboratory findings may include elevated ESR and CRP and mildly elevated WBC and platelet counts. Rheumatoid factor is negative and ANAs are absent except in psoriatic arthritis. HLA-B27 is common in enthesitis-related arthritis (>90% of patients) and may also be found in the other spondyloarthropathies, especially if sacroiliitis or anterior uveitis is present. Radiographic changes may include periarticular osteoporosis, changes associated with enthesitis (loss of sharp cortical margins, erosions, bony spurs), indistinct margins and erosions of the SI joints, sclerosis on the iliac side of the joint, and squaring of the corners of vertebral bodies (Fig. 110-3).
The primary treatment goals of the spondyloarthropathies are to control inflammation, minimize pain, and preserve function. NSAIDs, such as naproxen, may be sufficient. Sulfasalazine, intra-articular steroid injections, and biological medications may be helpful. Antibiotic treatment for reactive arthritis may be beneficial when C. trachomatis is the inciting cause. Physical therapy, along with education and exercise, plays an important role in maintaining function and flexibility. Patients with foot and ankle enthesitis may also benefit from custom fitted insoles.
JUVENILE IDIOPATHIC ARTHRITIS
JIA is a term that encompasses all forms of arthritis that begin before the age of 16 years, persist for more than 6 weeks, and have no identifiable cause. It is the most common chronic rheumatic disease in childhood. The International League of Associations for Rheumatology (ILAR) classification system includes seven disease categories based on the features present in the first 6 months of illness (Table 110-5).15–18 The underlying cause of JIA remains unclear but it appears to be a multifactorial immunopathogenic process in genetically susceptible individuals.15
Juvenile Idiopathic Arthritis (JIA): The ILar Classification System15–18
Arthritis is the common feature in all types of JIA that results in pain, loss of function and morning stiffness. Joint distribution and systemic symptoms vary based on the type of JIA.
Polyarticular disease involves five or more joints. It is further categorized as rheumatoid factor-positive (RF[+]) or rheumatoid factor-negative (RF[−]) with RF[−] polyarthritis having at least three distinct subsets. RF[+] polyarthritis includes the presence of IgM rheumatoid factor on at least two occasions, at least 3 months apart. RF[+] polyarthritis is the same as adult RF[+] polyarthritis and is mainly seen in adolescent female patients. At presentation, small joints of the hands and feet tend to be affected; if large joints are affected, it is usually in association with small joint disease. Many patients have involvement of the axial skeleton including the cervical spine; severe cases can result in atlantoaxial instability. Some patients have involvement of the cricoarytenoid joint, where it can result in hoarseness of the voice. The temporomandibular joint may also be affected. Boutonniere deformities (proximal interphalangeal joint flexion and distal interphalangeal joint hyperextension) and swan-neck deformities (proximal interphalangeal joint hyperextension and distal interphalangeal joint flexion) are common. Extra-articular manifestations include rheumatoid nodules in approximately 30% of patients and, much less frequently, aortic regurgitation.
RF[−] polyarthritis has a biphasic age of onset with an early peak between 2 and 4 years and a late peak between 6 and 12 years. Subsets include an early onset asymmetric arthritis that is associated with positive anti-nuclear antibodies (ANA), an increased risk of iridocyclitis, and a strong HLA association; a polyarthritis that presents in school-age children with symmetric large and small joint disease, an increased ESR, and a negative ANA; and a “dry synovitis” that is characterized by negligible joint swelling with significant joint stiffness, flexion contractures, and a normal or minimally elevated ESR.
In RF[+] and RF[−] polyarthritis, affected joints are swollen and warm, with minimal or no erythema. Although there is discomfort on range of motion, joint pain is generally not severe. Systemic involvement in polyarticular disease includes fever, irritability, and occasional hepatomegaly. In severe cases, significant growth disturbances can occur. RF[+] polyarticular disease is characterized by progressive, diffuse joint involvement with early radiographic changes, especially in the hands and feet. RF[−] polyarticular disease has a variable outcome depending on its subtype.
Oligoarticular arthritis involves four or fewer joints during the first 6 months of disease. In the ILAR criteria, patients are excluded from this category if they have psoriasis, a family history of psoriasis and HLA B27-associated illness in a first-degree relative, a positive RF test or if the disease occurs in a male patient older than 6 years. Knees are most commonly affected followed by the ankles, wrists, and elbows. Acute phase reactants may be normal or moderately increased; infrequently ESR is very high. Patients with oligoarticular arthritis are frequently ANA positive (70%–80%), may develop an asymptomatic iridocyclitis (30%), and have a strong association with some HLA alleles.15 Systemic manifestations of disease are generally mild. Patients may have persistent oligoarthritis in which the disease remains confined to four or fewer joints, or they may develop an extended oligoarthritis in which more than four joints become involved after the first 6 months. Risk factors for the development of extended oligoarthritis include ankle, wrist, or hand involvement, symmetric arthritis, arthritis of two to four joints and an elevated ANA titer and ESR.16
Systemic onset disease occurs throughout childhood. Diagnosis of systemic arthritis requires the presence of arthritis accompanied or preceded by at least 2 weeks of quotidian fever plus typical evanescent rash (discrete, circumcised, salmon-colored, 2- to 10-mm macules on the trunk and proximal extremities that typically coincide with fever), hepatomegaly, splenomegaly, generalized lymphadenopathy, or serositis. The onset of joint disease may be significantly delayed, which can obscure the diagnosis of JIA. Patients may be ill-appearing and have myalgias and abdominal pain during episodes of fever. Laboratory findings include leukocytosis with a preponderance of neutrophils, elevated liver enzymes, microcytic anemia, thrombocytosis, and very high ESR and CRP concentrations. The ANA titer is rarely positive.15 In approximately 50% of cases, systemic-onset JIA is associated with a relapsing-remitting course in which arthritis accompanies episodes of fever and remits when systemic features are controlled. In the other 50% of patients, it is associated with an unremitting, debilitating arthritis with few systemic symptoms. Other complications include the development of pericarditis, which in some cases can result in a clinically significant pericardial effusion, myocarditis, or pleuritis. Very infrequently, patients develop amyloidosis.
A rare but life-threatening complication of systemic JIA is macrophage activation syndrome. This is characterized by the sudden onset of sustained fever, pancytopenia, hepatosplenomegaly, liver insufficiency, coagulopathy, and neurologic symptoms. Pancytopenia, prolonged prothrombin and PTTs, elevated fibrin split products, hypertriglyceridemia, hyponatremia, and increased ferritin concentrations are present. The ESR is often low.
The differential diagnosis of JIA includes ARF, SLE, bacterial arthritis, reactive arthritis, and neoplastic diseases, especially leukemia. In the ED, the workup of suspected JIA includes a complete blood count, renal function studies, and a rapid streptococcal screening. Tests for ANAs and rheumatoid factors are indicated even though results are not immediately available. If a pyogenic arthritis is suspected, analysis of joint fluid is indicated. Patients with systemic-onset disease with evidence of myocarditis or pericarditis require an electrocardiogram and echocardiogram. Consultation with a pediatric rheumatologist is recommended and hospitalization (especially with systemic onset disease) may be necessary.
Although JIA tends to be a chronic illness, there has been great improvement in functional outcome over the past decade. Indicators of poor outcome include greater severity or extension of arthritis at onset, symmetrical disease, early wrist or hip involvement, presence of RF, persistent active disease, and early radiographic changes.19
The treatment of JIA consists of physical and occupational therapy to maintain and improve range of motion, muscle strength, and skills for daily activities. Splints may be used to prevent contractures. Aggressive treatment with NSAIDs is the initial treatment for most patients with JIA. For pauciarticular disease, intra-articular steroids may be used. For cases that do not respond to NSAIDs, glucocorticoids, cytotoxic drugs, or biological medications may be effective.20,21 Sulfasalazine is effective in patients with extended oligoarticular JIA and juvenile spondyloarthropathies. Pericarditis or myocarditis may respond to therapy with prednisone.20,21 Macrophage activation syndrome is treated with high-dose steroids and cyclosporin.
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