Kawasaki Disease: 2 Patients With Differing Clinical Presentations

Case 1

A 5-Year-Old Girl With Fever and Sloughing Skin

Vladimir A. Ljubimov, BS; Hazel L. Abinsay, MD; and Cynthia H. Ho, MD

A 5-year-old girl presented with a 2-week history of fever and rash. Peeling of the skin of her fingers and toes had been noted over the past 2 days.

On physical examination, the girl’s temperature was 38.9°C. She was tired but interactive. An erythematous tongue with prominent papillae (Figure 1) and desquamation of the hands and feet (Figures 2 and 3) were noted.

Kawasaki disease (KD) is an acute, systemic, medium-vessel, necrotizing vasculitis with a predilection for coronary arteries that presents in children 6 months to 5 years of age.¹ Its pathogenesis is unclear; however, the pattern of inflammatory response suggests that KD may represent a response to an intracellular viral pathogen.²

 The diagnosis of KD is made clinically, in cases of fever lasting more than 5 days, along with 4 of 5 of the following criteria: nonpurulent bulbar conjunctivitis, oral mucositis, hand and foot changes, unilateral cervical lymphadenopathy greater than 1.5 cm, and a polymorphous exanthem.¹ Incomplete KD is diagnosed with fewer than 3 of these criteria, along with suggestive laboratory findings such as elevated levels of acute-phase reactants, leukocytosis, anemia, sterile pyuria, elevated aminotransferase levels, hypoalbuminemia, or thrombocytosis. 

Echocardiographic findings such as coronary ectasia or aneurysms support the diagnosis of KD. Atypical KD refers to patients who fit the criteria for KD but who have a feature that is not usually seen in KD (eg, uveitis, nephritis).

 Oral mucosal changes occur in more than 90% of KD patients.³ Strawberry tongue represents prominent fungiform papillae on a background of inflamed glossal tissue.⁴ Discrete oral lesions such as vesicles, exudates, or ulcerations are unlikely due to KD.⁴

Extremity changes progress in stages. In the acute phase, vasodilation in the dermal papillary layer and capillary leak lead to the erythema and induration. Approximately 2 to 3 weeks after the onset of fever, desquamation of the periungual region occurs.¹ In severe cases, the palms and soles are affected.

 Treatment is high-dose intravenous immunoglobulin (IVIG) and aspirin, with better prognosis if treatment is initiated within the first 10 days of fever.¹ IVIG is recommended for patients who present late or have continued fever, elevated inflammatory markers, or coronary artery lesions.¹ Treatment may abate the inflammatory response but may not prevent the development of coronary artery lesions.⁵

 A high-dose aspirin (80-100 mg/kg) regimen is followed by low-dose aspirin (3-5 mg/kg) regimen for at least 6 weeks total.¹ Some practitioners continue high-dose aspirin until the patient has been afebrile for 48 hours, while others continue for 2 weeks regardless of fever status.¹ Low-dose aspirin is discontinued at 6 weeks if echocardiogram findings are normal. Patients with moderate to large aneurysms are started on a second antiplatelet agent such as clopidogrel or dipyridamole. Patients with giant aneurysms (> 8 mm) are started on a regimen of warfarin or low-molecular-weight heparin.¹

 In our patient, a transthoracic echocardiogram revealed coronary dilation at 4.5 mm. She was diagnosed with incomplete KD and treated with IVIG and aspirin. An echocardiogram performed 6 weeks after diagnosis showed resolution of the coronary dilation.

Vladimir A. Ljubimov, BS, is a student at the University of Southern California Keck School of Medicine in Los Angeles.

Hazel L. Abinsay, MD, is a resident in the departments of internal medicine and pediatrics at the Los Angeles County + University of Southern California Medical Center, Keck School of Medicine, in Los Angeles.

Cynthia H. Ho, MD, is a hospitalist in the departments of internal medicine and pediatrics at the Los Angeles County + University of Southern California Medical Center, Keck School of Medicine, in Los Angeles.

References

1. Newburger JW, Takahashi M, Gerber MA, et al. 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. Circulation. 2004;110(17):2747-2771.

2. Rowley AH, Shulman ST. Pathogenesis and management of Kawasaki disease. Expert Rev Anti Infect Ther. 2010;8(2):197-203.

3. Fukushige J, Takahashi N, Ueda Y, Ueda K. Incidence and clinical features of incomplete Kawasaki disease. Acta Paediatr. 1994;83(10):1057-1060.

4. Scardina GA, Fucà G, Carini F, et al. Oral necrotizing microvasculitis in a patient affected by Kawasaki disease. Med Oral Patol Oral Cir Bucal. 2007;12(8):E560-E564.

5. Muta H, Ishii M, Yashiro M, Uehara R, Nakamura Y. Late intravenous immunoglobulin treatment in patients with Kawasaki disease. Pediatrics. 2012; 129(2):e291-e297.

Case 2

A 4-Year-Old Girl With Fever and Neck Swelling

Brennan Forward, MD

A 4-year-old girl presented to the emergency department (ED) with a 1-day history of fever and right-sided neck swelling.

On physical examination, her temperature was 38.8°C, but all other vital signs were normal. She had a tender, firm mass on her right neck along the anterior cervical chain lymph nodes, measuring 6 cm in its longest diameter, with overlying erythema. No other lymphadenopathy was found. Range of motion of her neck was limited as a result of the swelling. Cardiac and respiratory examination findings were normal. Skin examination revealed no rashes or lesions.

The results of a contrast-enhanced computed tomography (CT) scan of her neck showed several enlarged cervical lymph nodes on the right side (Figures 4 and 5), and retropharyngeal soft tissue swelling on the right side. There was no abscess.

Laboratory evaluation showed an elevated white blood cell (WBC) count of 21,300/µL. The C-reactive protein (CRP) level was 145.5 mg/L. Results of rapid influenza and group A streptococcus tests were negative. She was given 50 mg/kg of ampicillin-sulbactam and admitted to the general pediatric ward with a diagnosis of cervical lymphadenitis.

During her hospitalization, the patient continued to be febrile, and her CRP level remained significantly elevated despite continued antibiotic therapy. On her fourth day of hospitalization, the infectious disease service was consulted, and antibiotic coverage was broadened with the addition of vancomycin; CT was repeated to evaluate for abscess formation. There was persistent thickening of the retropharyngeal tissues, but no abscess was identified.

On hospital day 6, the girl developed dry, cracked lips. On hospital day 8, she developed bilateral scleral injection. The following day (day 9 of fever), she developed a morbilliform rash on her legs, trunk, and arms. The diagnosis of KD was made based on clinical criteria (fever for more than 5 days, lymphadenopathy, bilateral nonpurulent conjunctivitis, cracked lips, and rash). IVIG and high-dose aspirin were given.

An echocardiogram revealed no coronary abnormalities. She remained afebrile after treatment with IVIG and aspirin. Her neck swelling, rash, and conjunctivitis resolved over the next 2 to 3 days. No abnormalities were found on a follow-up echocardiogram 2 weeks after discharge.

KD is characterized by vasculitis of medium-sized arteries, with a predilection for coronary arteries. KD is the leading cause of acquired heart disease in developed countries, although rheumatic heart disease continues to dominate in the developing world.¹

Because of the nonspecific symptoms and lack of a specific laboratory test, the diagnosis of KD is based on presence of fever at least 5 days concurrently with 4 of 5 clinical criteria: nonpurulent bulbar conjunctivitis, mucous membrane changes of the mouth, changes in peripheral extremities, a polymorphous exanthem, and cervical lymphadenopathy greater than 1.5 cm. However, only 40% of KD patients present with clinically fulfilled criteria.^2,3

Cervical adenopathy is the least common of the principal diagnostic criteria. Occasionally, KD manifests with fever and cervical adenopathy before other clinical signs appear.^4-7 These presentations may be misdiagnosed as bacterial cervical lymphadenitis, potentially delaying definitive treatment for KD and leading to serious cardiac sequelae.

Coronary artery lesions develop in 3% to 5% of children treated with IVIG, and up to 25% of untreated children.¹ It is not known whether children who have normal-appearing coronary arteries during the acute phase of the disease will be at risk for endothelial dysfunction and accelerated atherosclerosis later in the life.

Clinicians who treat febrile children with cervical adenopathy should keep KD in their differential diagnosis. In febrile patients with cervical adenitis who are not responding to antibiotic therapy as expected, be vigilant for symptoms or laboratory values that might suggest KD.

Brennan Forward, MD, is a pediatrician at Sanford Pediatrics in Moorhead, Minnesota.

References

1. Son MBF, Newburger JW. Kawasaki disease. Pediatr Rev. 2013;34(4):151-162.

2. Kritsaneepaiboon S, Tanaanantarak P, Roymanee S, Lee EY. Atypical presentation of Kawasaki disease in young infants mimicking a retropharyngeal abscess. Emerg Radiol. 2012;19(2):159-163.

3. Park AH, Batchra N, Rowley A, Hotaling A. Patterns of Kawasaki syndrome presentation. Int J Pediatr Otorhinolaryngol. 1997;40(1):41-50.

4. Kanegaye JT, Van Cott E, Tremoulet AH, et al. Lymph-node-first presentation of Kawasaki disease compared with bacterial cervical adenitis and typical Kawasaki disease. J Pediatr. 2013;162(6):1259-1263.

5. Kao H-T, Huang Y-C, Lin T-Y. Kawasaki disease presenting as cervical lymphadenitis or deep neck infection. Otolaryngol Head Neck Surg. 2001;124(4):468-470.

6. Kubota M, Usami I, Yamakawa M, Tomita Y, Haruta T. Kawasaki disease with lymphadenopathy and fever as sole initial manifestations. J Paediatr Child Health. 2008;44(6):359-362.

7. Nomura Y, Arata M, Koriyama C, et al. A severe form of Kawasaki disease presenting with only fever and cervical lymphadenopathy at admission. J Pediatrics. 2010;156(5):786-791.