A 3-year-old boy presents for his second visit to see you. Two days ago he was seen with a 4-day history of intermittent fever spiking to 104°F (40°C) and irritability. His examination at that time was remarkable for bilateral conjunctivitis, oropharyngeal injection, and red cracked lips. He drank 4 oz of an electrolyte solution in the clinic and was sent home with instructions for symptomatic care. Today he returns with persistent fever and irritability. The physical findings noted previously are still present, but now he also has a maculopapular truncal rash, hand and foot edema, and an enlarged but nonsuppurative right anterior cervical lymph node.
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 60: Kawasaki Syndrome
Summary: A 3-year-old boy with high-spiking fevers and irritability of 6 days’ duration. Conjunctivitis, unilateral anterior cervical lymphadenopathy, oropharyngeal erythema, red cracked lips, a maculopapular rash, and edema of the hands and feet are present on examination.
• Most likely diagnosis: Kawasaki syndrome (KS; mucocutaneous lymph node syndrome).
• Best diagnostic test: No laboratory study is diagnostic. Echocardiography is used to monitor for coronary aneurysm development, the most serious potential disease complication. Elevated acute-phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), normocytic anemia, and thrombocytosis support the diagnosis.
• Treatment: Early anti-inflammatory therapy with high-dose intravenous immunoglobulin (IVIG) and aspirin reduces the risk of coronary complications.
1. Know the diagnostic criteria for KS.
2. Recognize the need for early diagnosis and treatment to prevent coronary complications.
3. Be familiar with other diagnostic possibilities in the differential diagnosis of KS.
Diagnosing KS can be difficult in the first few days of illness, when only a few classic clinical findings may be present. Adenoviral infection was perhaps the presumptive diagnosis at the first visit, although the intermittent fevers for 4 days and irritability might have prompted suspicions of another etiology. His diagnosis became more obvious on the sixth illness day when he manifested additional clinical signs, although other conditions still must be considered.
Fever and Rash
HYDROPS OF GALLBLADDER: When the wall of the gallbladder becomes acutely distended without presence of stone or inflammation; commonly associated with KS, group A streptococcal infection, leptospirosis, or Henoch-Schönlein purpura.
POLYMORPHOUS RASH: An exanthem that may take various forms among affected individuals, such as maculopapular, erythema multiforme, morbilliform, or scarlatiniform.
STRAWBERRY TONGUE: Erythema of the tongue with prominent papillae, typically seen only in scarlet fever, KS, and toxic shock syndrome.
THROMBOCYTOSIS: Elevation of the platelet count above 450,000/mm3. In KS this usually occurs after the 10th day of illness and may last for a few weeks.
Kawasaki syndrome is a generalized vasculitic disease of medium-sized arteries associated with fever and exanthem of unknown etiology, but is thought to be infectious. The incidence is highest among Asians, but it is seen worldwide. It occurs most frequently in children younger than 5 yearsand slightly more frequently in boys than in girls. It is the most common cause of acquired heart disease in American children.
The diagnosis of KS is based on finding the characteristic signs (Table 60-1), although children with fewer signs who later develop coronary artery disease (CAD) are recognized. Cervical adenopathy is seen less frequently than the other diagnostic criteria, occurring in 30% of patients; while conjunctivitis occurs in over 90% of the children. Incomplete disease occurs most frequently in infants, the group most likely to develop coronary complications. Although no test establishes the diagnosis, certain laboratory findings are characteristic. The ESR and CRP are elevated, and normocytic anemia and leukocytosis are common. The platelet count is usually normal initially but often rises above 500,000 by the 10th day. Sterile pyuria, cerebrospinal fluid pleocytosis, and mildly elevated hepatic transaminase levels are the most commonly seen abnormalities when other organ systems are involved. Other gastrointestinal symptoms may include abdominal pain, right upper quadrant pain, and vomiting (which can also be symptoms of hydrops of the gallbladder). Patients can have arthralgias, arthritis, or anterior uveitis. Cardiac echocardiography may identify abnormalities of the coronary arteries, valves, pericardium (effusion), or myocardium (congestive heart failure). The differential diagnosis of KS includes infectious and noninfectious conditions, such as streptococcal disease, staphylococcal toxin (toxic shock syndrome), rickettsial infection, measles, Epstein-Barr virus infection, drug hypersensitivity reactions, systemic-onset juvenile idiopathic arthritis, and leptospirosis.
Table 60-1 • DIAGNOSTIC CRITERIA FOR KAWASAKI DISEASE
Figure 60-1. A child with Kawasaki disease with cherry red and hemorrhagic fissuring of the lips, an erythematous exanthema, and edema of the fingertips. (Reproduced, with, permission from Wolff K, Johnson RA. Fitzpatrick’s Color Atlas and Synopsis of Clinical Dermatology. 6th ed. New York, NY: McGraw-Hill; 2009. Figure 14-44.)
Successful treatment depends on rapidly starting high-dose aspirin and IVIG. Rapid defervescence in the next 2 to 3 days generally occurs with this regimen. Aspirin therapy is later reduced from anti-inflammatory to antithrombotic doses and continued until 6 to 8 weeks after disease onset, when the ESR normalizes. Children with coronary artery disease require prolonged antithrombotic therapy.
Even with treatment, approximately 5% of children develop coronary artery dilation, and 1% develop giant aneurysms. Without treatment in the first 10 days, fever tends to persist and 25% of children will develop aneurysms. Aneurysm risk factors include male gender, prolonged fever, age younger than 12 months, higher baseline neutrophil and band counts, lower hemoglobin level, and platelet count less than 350,000/mm3. Children without known cardiac sequelae during the first month return to their normal state of health; those with persistent cardiac abnormalities may suffer significant morbidity. Death is rare and is caused by myocardial infarction or, less commonly, aneurysm rupture.
60.1 A 12-month-old child arrives for a well-child examination. He was hospitalized 2 months ago for KS and was taken off aspirin therapy 6 weeks prior to this visit. His most recent echocardiogram was normal. For this patient, special consideration should be paid to which of the following?
A. His developmental assessment
B. The abdominal examination
C. Live-vaccine administration
D. Serum hemoglobin evaluation
E. Assessment of possible lead toxicity
60.2 A 15-month-old child is on long-term aspirin therapy for coronary artery abnormalities that resulted from KS. In addition to his routine vaccinations required for school, he should receive which of the following?
A. Pneumococcal vaccine
B. Influenza vaccine
C. Meningococcal vaccine
D. Oral polio vaccine
E. Varicella vaccine
60.3 A 5-month-old irritable infant develops 3 days of high fever, a maculopapular diaper rash, and swollen, red lips. He has a mild normocytic anemia and a white blood cell count (WBC) of 15,000/mm3with a predominance of neutrophils and immature forms. Urinalysis is normal, but the cerebrospinal fluid shows a pleocytosis with a negative Gram stain. After 24 hours of ceftriaxone, he continues to have high fever and has developed foot edema. Subsequent management of this child should include which of the following?
A. Nystatin for the diaper rash
B. Repeat of the spinal tap
C. Addition of vancomycin to the antibiotic regimen
D. Pediatric cardiology consultation; beginning of IVIG infusions and oral high-dose aspirin
E. Continuing current management and following the culture results
60.4 Who of the following children with KS is at greatest risk for coronary artery disease?
A. A 5-year-old boy with 6 days of high fever, sterile pyuria, a truncal rash, and strawberry tongue
B. A 3-year-old girl with 5 days of high fever and cerebrospinal fluid pleocytosis
C. A 2-year-old girl with 5 days of high fever and an initial ESR of 80 mm/h
D. A 1-year-old boy with 6 days of high fever, a maculopapular rash, and mildly elevated hepatic transaminase levels
E. A 6-month-old boy with 11 days of high fever and a small pericardial effusion on initial echocardiogram
60.1 C. Live-virus vaccines (measles-mumps-rubella [MMR], varicella) are delayed for 11 months following high-dose IVIG administration; IVIG potentially interferes with the immune response. The measles vaccine, typically given as MMR at 12 months, is provided if the exposure risk is high, but reimmunization is required unless serologic testing indicates adequate antibody titers.
60.2 B. Children on prolonged aspirin therapy receive the influenza vaccine; they are at increased risk of Reye syndrome if they are infected and taking aspirin. Reye syndrome is composed of acute encephalopathy and liver dysfunction with one-third of affected children dying from the disease; it seemed to be linked to children with a viral illness, especially influenza, who took aspirin during the illness. While often not required for day care or school attendance, the Centers for Disease Control and Prevention recommends that all children aged 6 months and older receive an annual influenza vaccine.
60.3 D. This child’s initial presentation is consistent with, but not diagnostic of, KS (Table 60-1). His persistent fever and peripheral extremity edema increase the possibility of KS and should prompt further investigation and treatment.
60.4 E. Risk factors for development of coronary aneurysms include male gender, fever for more than 10 days, age younger than 12 months, low serum albumin or hemoglobin level, early cardiac findings (eg, mitral regurgitation or pericardial effusion), and thrombocytopenia.
The diagnosis of Kawasaki syndrome (KS) is based on clinical criteria and should be strongly suspected in a young child with a combination of high fever for more than 4 days, oropharyngeal changes, conjunctivitis, extremity changes, rash, and cervical adenopathy.
Children with incomplete disease (“atypical KS”) can develop coronary artery abnormalities.
The most important complication of KS is coronary artery disease. A pediatric cardiologist usually is involved in the care of these children.
Early recognition and initiation of therapy for KS is key to preventing potential coronary complications.
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