A 3-year-old boy has a 20-day history of high fevers that spike twice daily. He was diagnosed with otitis media on the fifth day of fever and was prescribed amoxicillin, but the fever persisted. The fever is associated with a faint rash on the trunk and proximal extremities and complaints of “body aches.” A chest radiograph is normal, but a complete blood count (CBC) shows a hemoglobin of 9.8 mg/dL, a hematocrit of 29.9%, a white blood cell count of 18,000/mm3, and a platelet count of 857,000/mm3. He has developed an aversion to bearing weight and continues to have fevers to 102.5°F (39.2°C), but otherwise he has normal vital signs. His examination is remarkable for scattered lymphadenopathy, hepatosplenomegaly, and mild swelling of his interphalangeal joints and knees.
What is the most likely diagnosis?
What is the best diagnostic test for this disorder?
What is the treatment for this condition?
ANSWERS TO CASE 26: Juvenile Idiopathic Arthritis (JIA)
Summary: A 3-year-old boy has 20 days of high-spiking fevers and a rash and “body aches” that wax and wane with the fevers. He also has a 1-day history of refusal to bear weight. His examination is significant for lymphadenopathy, organomegaly, and joint swelling. His chest radiograph is negative, but the CBC reveals leukocytosis, thrombocytosis, and anemia.
• Most likely diagnosis: Systemic-onset juvenile idiopathic arthritis (JIA; previously termed juvenile rheumatoid arthritis).
• Best diagnostic test: No laboratory studies are diagnostic for JIA, but a history plus a CBC, blood cultures, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antinuclear antibody (ANA), and synovial fluid assessment can aid in establishing or eliminating this diagnosis.
• Treatment: Nonsteroidal anti-inflammatory drugs (NSAIDs), methotrexate, and glucocorticoids can be used to control symptoms. Physical and occupational therapy are important for preserving function and preventing deformity.
1. Know the three forms of JIA and their most common presenting signs and symptoms.
2. Recognize systemic-onset JIA as an important consideration in the evaluation of childhood fever of unknown origin (FUO).
The differential diagnosis for childhood FUO is long and includes infectious, hematologic, and rheumatologic causes. The fever pattern can sometimes aid in narrowing the diagnostic possibilities. In this case, the daily high-spiking fevers associated with a characteristic rash are suggestive of systemic JIA. Organomegaly and lymphadenopathy also are characteristic of systemic JIA. Arthritis may develop after other symptoms begin, as in this case, sometimes appearing months or even years into the disease course. For cases where arthritis first appears late in the disease course, leukemia may be a consideration.
Juvenile Idiopathic Arthritis
ARTHRALGIA: Any pain that affects a joint.
ARTHRITIS: Swelling or effusion of a joint, or the presence of two or more of the following signs: limited range of motion, tenderness or pain on motion, and increased heat in one or more joints.
SYSTEMIC-ONSET JIA: Characterized by arthritis with fever, evanescent rash, hepatosplenomegaly, serositis, and lymphadenopathy.
OLIGOARTICULAR JUVENILE IDIOPATHIC ARTHRITIS (OLIGOARTHRITIS): JIA with involvement of one to four joints.
POLYARTICULAR JUVENILE IDIOPATHIC ARTHRITIS (POLYARTHRITIS): JIA with involvement of five or more joints.
Juvenile idiopathic arthritis is the most common rheumatologic disorder in children. The diagnosis specifies onset prior to the age of 16 years and symptom duration of 6 weeks or longer. Other causes of arthritis in children (infectious and other rheumatologic causes) must be excluded; in the sexually active adolescent, gonococcal arthritis must be considered. Three diverse entities fall under the JIA rubric, classified according to symptoms occurring in the first 6 months of illness: (1) systemic-onset disease, (2) polyarticular disease, and (3) oligoarticular disease.
Systemic symptoms dominate the clinical scene in systemic-onset JIA, making the diagnosis difficult if frank arthritis is not present. Daily high-spiking fevers for 2 weeks or more, a rash and arthralgias that wax and wane with the fever, lymphadenopathy, and organomegaly are characteristic of systemic-onset disease. Pericarditis, hepatitis, pleural effusion, and encephalopathy also may occur.
Polyarticular disease is diagnosed when five or more joints are involved and systemic signs and symptoms are mild or absent. This disease is more common in girls and has a biphasic age of onset (most cases occur at ages 1 to 3 years and the remainder occur at ages 9 to 12 years). The younger patients are usually RF negative, while the older age group is often RF positive. The presence of this factor tends to cause a disease presentation similar to adult rheumatoid arthritis. The cervical spine, temporomandibular joints, shoulders, and hips are the most commonly affected joints.
Oligoarticular JIA is the most common form and involves fewer than five joints. It is divided into persistent and extended categories; extended refers to the disease progressing to affect more than four joints after the first 6 months. Oligoarthritis occurs predominantly in toddler-aged females, and serum ANA often is positive. The knee is most commonly affected, followed by the ankle. It is crucial for these children to have frequent ophthalmologic screenings as one-fourth of them will develop asymptomatic iridocyclitis (iris and ciliary body inflammation; also called “anterior uveitis”). Eye disease does not parallel the arthritis activity.
The initial laboratory evaluation for the child with suspected systemic JIA includes a CBC, ESR, and blood cultures. Leukocytosis, thrombocytosis, and anemia support the diagnosis of systemic JIA. The ESR is elevated, and blood cultures are negative. Evaluation of synovial fluid may be necessary to rule out septic arthritis, particularly in the presence of exquisitely tender joints or when only a single joint is involved. Rheumatoid factor and ANA usually are negative in systemic JIA.
Medications for JIA include NSAIDs, steroids, methotrexate, and other immunosuppressive agents. Physical and occupational therapy are vital for maintaining joint function and preventing further deformities. Routine slit-lamp ophthalmic examinations to monitor for uveitis are indicated. Approximately 50% of children will have their JIA persist into adulthood.
26.1 A 14-year-old girl has a 1-week history of arthritis involving her hands, wrists, knees, and ankles. At the onset she had noted that her cheeks seemed flushed; this resolved and has been followed by a slightly pruritic red macular rash over her torso and proximal extremities that is now clearing in some areas. On review of systems, she reports rhinorrhea and a low-grade fever 2 weeks ago. On examination, she has tender swelling of the aforementioned joints and an erythematous macular rash with a reticular pattern. Which of the following findings would help identify the most likely diagnosis?
A. Positive rheumatoid factor
B. Reticulocyte count of 0%
D. Skin biopsy of the rash
E. Synovial fluid analysis
26.2 A 5-year-old girl is referred to a pediatric rheumatologist with a 4-week history of mild swelling and decreased range of motion in the left knee and right elbow. She is afebrile and appears otherwise well. Positive findings on which of the following evaluations will be most helpful in establishing her diagnosis?
B. Complete blood count
C. Computerized tomographic scan of the involved joints
D. Slit-lamp examination of her eyes
E. Bone scan
26.3 A 6-year-old boy presents with his mother after developing acute right groin and knee pain that causes him to limp. He and the mother do not recall any trauma. Review of systems is positive only for rhinorrhea and sore throat 2 weeks ago. On examination, he is afebrile and his knee exam is normal, but he walks with a right toe-touch gait. Which of the following are the most appropriate next steps in his evaluation?
A. Assess range of motion of the right hip; measure WBC and ESR; perform ultrasound of the right hip.
B. Perform ophthalmologic exam; measure ANA and RF; perform x-ray of the knee.
C. Perform a full skin exam; interview the child alone about abuse; perform a skeletal survey.
D. Ask the mother about bleeding disorders; measure coagulation factors; perform aspiration of the knee.
E. Interview the child and mother about recent school stressors; provide reassurance to the mother that he is exaggerating growing pains for secondary gain; refer to counseling services.
26.4 A 3-year-old boy with suspected systemic-onset JIA develops tachycardia and dyspnea on the fifth hospital day. He complains that his chest hurts. Heart auscultation reveals a “friction rub” sound. Which of the following is the next best step in management?
A. Give him a nebulized albuterol treatment.
B. Give him a dose of furosemide.
C. Give him some acetaminophen.
D. Check his oxygenation status through pulse oximetry, obtain a stat electrocardiogram, and consult with a pediatric cardiologist.
E. Check his oxygenation status via pulse oximetry, obtain a stat chest x-ray, and initiate intravenous antibiotics.
26.1 B. The differential diagnosis for childhood arthritis includes infectious and rheumatologic disorders. Her symptoms and physical examination findings are typical of parvovirus B19 infection. Patients with this infection can have a transiently positive RF and often will have mild anemia. Parvovirus B19 targets erythroid precursors; there is no compensatory reticulocytosis as these are lysed by the virus. The other studies would not be helpful in distinguishing the etiology of the arthritis.
26.2 D. JIA is the most common cause of uveitis in children. Uveitis onset may be insidious, and may be the only initial manifestation of JIA. The disease is more common in young girls. Slit-lamp findings include band keratopathy, posterior synechiae, and cataracts. Children with JIA should have periodic slit-lamp examinations in order to detect eye disease early. Consideration may be given to obtaining the tests suggested in the other answer choices, but positive results on these tests are unlikely to be specific for JIA.
26.3 A. A good rule of thumb is to examine one joint above and one joint below the site of symptoms. Hip pain may refer to the groin, anterior thigh, or knee. If the hip’s range of motion is near-normal, WBC and ESR are normal, and ultrasound shows a joint effusion, the most likely diagnosis is transient (toxic) synovitis of the hip.
26.4 D. A friction rub is characteristic of pericarditis, which is a common and serious complication of systemic-onset JIA. The friction rub is a “grating” or “creaking” sound that often is best heard along the left sternal border. Patients typically complain of chest pain that is relieved when the patient is asked to lean forward, and worsened by deep inspiration or coughing; however, pain is not always present. Rarely, pericarditis in JIA may precede the development of arthritis by months or even years. Low-voltage QRS complexes and ST-segment elevation may be seen on the electrocardiogram. Treatment consists of salicylates or steroids.
The spectrum of juvenile idiopathic arthritis comprises three entities: (1) systemic-onset disease, (2) polyarticular disease, and (3) oligoarticular disease.
Systemic-onset juvenile idiopathic arthritis is an important consideration in the differential diagnosis of childhood fever of unknown origin.
The diagnosis of juvenile idiopathic arthritis is based on clinical criteria and by the exclusion of other possibilities; no single laboratory test confirms the diagnosis.
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