Author: Shelby Chesbro, MS6 | UMKC School of Medicine
Column Editor: Angela Myers, MD | Director, Division of Infectious Diseases | Associate Director, Infectious Diseases Fellowship Program | Associate Professor of Pediatrics, UMKC School of Medicine
A previously healthy 2-month-old female presented to the emergency department with a maculopapular rash that started approximately one day before and spread cephalocaudally. She had associated dry cough, rhinorrhea, poor oral intake and two days of fever up to 102.8° refractory to acetaminophen. The patient was tachycardic with a heart rate of 200 without response to fluid resuscitation. On physical examination she had bilateral non-exudative conjunctivitis.
Which of the following is the most appropriate next step?
A. Abdominal ultrasound
B. Obtain echocardiogram
C. MRI brain
D. Urine culture
The correct answer is B.
Further testing revealed dilated coronary arteries on echocardiogram with negative evaluation for bacterial and viral pathogens. These findings lead to the diagnosis of Kawasaki disease (KD) shock syndrome. The rash, conjunctivitis and fever are nonspecific and could represent several disease processes including measles, adenovirus, KD and others. However, KD should always be considered in any child ≤6 months of age with ≥5 days of fever, even if the physical stigmata of KD are absent.
KD is a self-limited vasculitis of the medium-sized arteries which can manifest in many different organ systems. The presentation is similar to a viral illness, which can make the diagnosis challenging. To diagnose classic (or complete) KD, the patient must have ≥5 days of fever (≥101°F) in addition to ≥4 of the following clinical criteria:
- Bilateral limbic-sparing, non-exudative conjunctival injection
- Erythema and cracking of lips, strawberry tongue, and/or erythema of oral and pharyngeal mucosa
- Generalized erythematous rash which may be morbilliform, maculopapular, scarlatiniform or erythema multiforme
- Erythema of the palms and soles or firm induration of the hands and feet
- Anterior cervical lymphadenopathy with at least one node >1.5cm, often unilateral
In patients with two to three clinical criteria, along with elevated inflammatory markers (C-reactive protein ≥3.0 mg/dL and/or erythrocyte sedimentation rate ≥40 mm/hr), a diagnosis of incomplete KD should be considered. Presence of three of the following should prompt diagnosis:
- Urine ≥10 WBC/HPF
- Elevated ALT levels
- WBC count ≥15,000/mm3
- Anemia for age
- Platelet count ≥450,000 after the 7th day of fever
- Albumin ≤3 g/dL
The presence of fever with coronary artery dilation (z score >2.5) is diagnostic of KD regardless of clinical and laboratory findings. Coronary artery aneurysm is a serious complication that occurs in up to 25% of untreated children, but only <5% of children treated within 10 days of fever onset. Infants <12 months old and patients with initial thrombocytopenia are at higher risk for aneurysms. Long-term sequela following coronary aneurysm includes myocardial and/or valvular dysfunction.
KD can present with shock during the acute phase, termed KD shock syndrome. An evaluation for sepsis is vital to rule out both bacterial and viral etiologies before the shock may be attributed to KD. This presentation is uncommon, but is associated with higher rates of cardiovascular complications and refractory disease.
Treatment during the acute phase is focused on decreasing the inflammation of the medium-sized arteries. The mainstay of therapy is moderate to high-dose aspirin and Intravenous Immune Globulin (IVIG). Aspirin is continued through follow-up and echocardiogram evaluation, which typically occurs over the subsequent six to eight weeks. Patients may continue to be febrile after initial IVIG treatment, which may require a second dose of IVIG or other therapies including infliximab or corticosteroids. The patient above required two doses of IVIG and one dose of infliximab, and her coronary artery dilation resolved on subsequent echocardiogram.
Although rare in patients with KD, the use of aspirin and development of febrile illnesses, particularly influenza, has been associated with Reye syndrome. Therefore, all family members >6 months of age should have an influenza vaccine and caution should be given to family members to seek prompt treatment if their child begins to develop influenza-like symptoms.