A 4-year-old African American boy presented to the emergency department (ED) for evaluation of a generalized pruritic rash that had started on his face and had progressed to involve his entire body. The rash had first appeared 13 days ago and had prompted a visit to the ED, at which time a throat culture and rapid strep test were done; he was started on a 10-day course of cephalexin. Despite the antibiotics, the rash spread and was followed by a low-grade fever for the next 6 days, but his temperature had not been recorded at home.
At the current presentation, the boy appeared alert and playful and was afebrile, despite the itchy rash. The boy, who is adopted, had a known history of eczema, mild intermittent asthma controlled with albuterol as needed, and a seizure disorder of unknown origin controlled with levetiracetam. The boy had no history of nausea, vomiting, swelling, joint pain, red eyes, runny nose, cough, or pulling of the ears.
His vital signs were within normal limits, with no significant findings on systemic examination. However, general examination revealed a papular, generalized, nontender, and pruritic rash, with peeling noted over the bilateral inguinal regions. The boy was admitted to the hospital for further evaluation, and he was given diphenhydramine for the pruritus and Aquaphor ointment for the eczematous rash.
Results of a complete blood count (CBC) were normal, with an erythrocyte sedimentation rate (ESR) of 51 mm/h. The results of a basic metabolic panel, urinalysis, blood culture, and antistreptolysin O titer tests were normal, as were levels of aspartate aminotransferase, total protein, serum albumin, and direct bilirubin. However, the test results showed an elevated C-reactive protein (CRP) level of 43 mg/dL, an elevated alanine aminotransferase level of 72 U/L, and an elevated alkaline phosphatase level of 364 U/L.
Answer: Kawasaki diseaseSee the full case at Consultant360
Fever with rash is among the most common pediatric presentations and has a spectrum of possible diagnoses. The generalized, nontender, and papular nature of this boy’s initial eruption, along with his low-grade fever, led to a clinical suspicion of scarlet fever at the first ED visit. Given the bacterial etiology of scarlet fever, and that it can lead to sequelae such as rheumatic fever and glomerulonephritis, an antibiotic was started at that time before the return of throat culture results, which eventually were shown to be negative for streptococci.
The boy’s fever eventually subsided, and the rash became desquamating, localized over the bilateral inguinal region. The rash’s having turned pruritic and scaly was suspected to be secondary to eczema or to be an adverse effect of the levetiracetam.
The elevated markers of systemic inflammation and the unrecorded low-grade fever that had persisted for 6 days led to suspicion of incomplete Kawasaki disease. In accordance with the algorithm for evaluation of suspected incomplete Kawasaki disease,1 an echocardiogram was immediately ordered, the results of which showed mild ectasia of the left main and left anterior descending coronary arteries. A clinical diagnosis of Kawasaki disease was made.
The boy immediately received intravenous immunoglobulin (IVIG), given slowly over 12 hours, and high-dose aspirin. The boy was found to be sensitive to IVIG therapy. His levetiracetam was continued at the usual dosage, and his vital signs were monitored every 4 hours. ESR and CRP were measured daily.
On the second day of hospitalization, CBC results were normal, but the ESR had increased to 68 mm/h, and the CRP level had decreased to 18 mg/dL. Due to the persistent elevation of systemic markers of inflammation, he was started on a second dose of IVIG. On the third hospital day, his ESR had increased to 98 mm/h, and his CRP level was 19 mg/dL. On day 4, the ESR was 78 mm/h, and the CRP level was 7.7 mg/dL. On the fourth day, he was afebrile, playful, and alert, and he was discharged on continuous aspirin therapy with follow-up echocardiography scheduled for after 2 weeks later.
Kawasaki disease (KD) is a self-limiting, acute-onset, febrile, vasculitic disorder that is common in younger children. Its etiology remains largely unknown. The presentation of KD mimics a variety of childhood illness. The diagnosis is clinical and is based on the presence of fever for 5 or more days, with at least 4 of the 5 following features:
• Peripheral membranous desquamation of the fingertips and toe tips, or transverse grooves across the fingernails and toenails (Beau lines), preceded by swelling of palms and soles
• A polymorphous and nonvesicular rash typically occurring as perineal erythema and desquamation. (An interesting finding is that redness or crust formation at the site of bacille Calmette-Guérin [BCG] inoculation is seen in children from countries where the BCG vaccine is given routinely).
• Oropharyngeal changes such as erythema, fissuring, and crusting of the lips; strawberry tongue; and diffuse mucosal injection of the oropharynx
• Bilateral, bulbar conjunctival injection
• Acute nonpurulent cervical lymphadenopathy
These signs do not always appear together; therefore, other nonspecific findings that are not part of the diagnostic criteria also should be keenly looked for. These signs and symptoms include diarrhea, vomiting, abdominal pain, hepatic dysfunction, arthritis, central nervous system irritability with aseptic meningitis, and cardiovascular abnormalities.
Abnormal laboratory test findings are not a part of the traditional diagnostic criteria for KD; however, their presence can help immensely in supporting the diagnosis of atypical KD, which usually includes some of the classical features of KD but not enough of them to meet the case definition.
For incomplete or atypical KD, fever for more than 5 days with 2 or 3 of the clinical criteria mentioned above, along with supporting evidence of elevated markers of systemic inflammation, are significant enough findings to proceed to echocardiography.2 Inflammatory markers include elevated acute-phase reactants (eg, CRP or ESR), thrombocytosis developiong after the seventh day of illness, leukocytosis, and a left shift (increased immature neutrophils) in the white blood cell count. Children with KD often present with a normocytic, normochromic anemia.
Echocardiography is the study of choice to evaluate for coronary artery aneurysms. Serial echocardiograms should be obtained at the time of diagnosis, at 2 weeks, and at 6 to 8 weeks after the onset of the illness. Echocardiography findings can include congestive heart failure, myocarditis, pericarditis, valvular regurgitation, coronary artery aneurysms, or other significant coronary artery abnormalities.2
The early course of KD often is mistaken for simple childhood illnesses such as viral gastroenteritis, viral upper respiratory tract infection, or pneumonia, depending on additional presenting symptoms such as vomiting or cough. Other differential diagnoses are scarlet fever, drug-induced rash, measles, erythema infectiosum (fifth disease), toxic shock syndrome, and juvenile idiopathic arthritis.
Treatment with high-dose IVIG, 2 g/kg, is the mainstay of therapy, since the main goal is to reduce the prevalence of coronary artery aneurysms. IVIG should be given promptly and within the first 7 days of the illness. Aspirin at high dose (80-100 mg/kg/d) in 6 divided doses for a variable period, followed by a once daily low dose of antithrombotic (3-5 mg/kg/d) traditionally has been the standard, as well. Despite the risk of Reye syndrome with the use of aspirin in the pediatric population, its use in KD treatment is an exception. For patients who are resistant to IVIG therapy, infliximab (a tumor necrosis factor inhibitor) or a calcineurin inhibitor such as cyclosporin A can be effective.
Trishna Sharma, MBBS, is a research volunteer at the NYU Langone Medical Center Institute for Social and Psychiatric Initiatives—Research, Education and Services (InSPIRES) in New York, New York.
Parag Bhattarai, MD, is an emergency medicine pediatrician at Cape Fear Valley Medical Center in Fayetteville, North Carolina.
Manu Sharma, MD, is a pediatrician at KidzCare Pediatrics in Hope Mills, North Carolina.
Riwaaj Lamsal, MD, is a pediatrician at the Brooklyn Hospital Center in Brooklyn, New York.New York.
1. Newburger JW, Takahashi M, Gerber MA, et al; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics. 2004;114(6):1708-1733.
2. Son MB, Newburger JW. Kawasaki disease. Pediatr Rev. 2013;34(4):151-162.