A case of recurrent Kawasaki disease

Ronald P. Januchowski, DO, VCOM, Family Medicine Program, Spartanburg Regional Medical Center, 853 N. Church Street, Suite 510, Spartanburg, SC 29303-3077.

E-mail address: rjanuchowski@srhs.com.

Kawasaki disease is classified as a rare form of vasculitis especially affecting the coronary arteries of children under the age of five years with no known infectious agent of origination. The clinical diagnosis of Kawasaki disease is made on the basis of a five-day history of persistent fever of unknown origin that is resolved after empirical treatment with antibiotics, and clinical presentation of at least five of the diagnostic criteria.1 Kawasaki disease, also known as mucocutaneous lymph node syndrome, is a rare diagnosis found most often among children of Japanese descent. It affects 150 per 100,000 children of Japanese descent younger than five years, and in the United States it affects 10 to 15 children per 100,000 younger than five years.2 This disease, if diagnosis is delayed, is a leading cause of cardiac catastrophe and sudden death in young children via coro- nary artery aneurysm.3 Recurrent Kawasaki disease usually occurs on average between two to four years from initial diagnosis. The incidence of recurrent Kawasaki disease worldwide is 2.3%3 and in the United States 0.8%.4 In this case report, the patient presented with a recurrence of Ka- wasaki disease five months after initial diagnosis.

‌Case summary

The patient in this case report was a two-year, ten-month- old African-American female that presented to the emer- gency department with a one-week history of high fever, with a maximum temperature of 103°F; sore throat; bilateral eye conjunctivitis; nasal congestion; swollen hands and feet; blotchy skin; and desquamation of the genital area. The child also had a history of no solid food intake for one week, but adequate fluid intake per the patient’s mother. In addi- tion, the child had two to three watery diarrhea episodes daily for three days with a decreased number of wet diapers. The patient’s mother stated symptoms were identical to when the patient was first diagnosed with Kawasaki disease, five months before this presentation. The patient was treated with intravenous gamma globulin and oral aspirin and re- covered without sequelae at that time.

The initial physical examination revealed an ill-appear- ing febrile child. The patient weighed 12.7 kilograms. Her vital signs included an oral temperature of 101.5°F, a heart rate of 155 beats per minute, a respiratory rate of 18 breaths per minute, and a blood pressure of 105/63 mm Hg. The patient had bilateral nonexudative conjunctivitis; erythem- atous lips and oral mucosa; and dry, cracked lips. Slight edema and erythema of the hands and feet were noted bilaterally. No prominent cervical lymph nodes were pal- pated. There was desquamation of the genital area. There were no abnormalities noted on cardiovascular, pulmonary, or gastrointestinal physical examination. Complete labora- tory data is found in Fig. 1.

Prophylactic antibiotics were initiated to cover possible meningitis. These antibiotics were discontinued once lum- bar puncture results were negative for bacterial meningitis. Given the laboratory studies, radiographs, and echocar- diogram results, the differential diagnosis was revised to include fever of unknown origin and aseptic meningitis, with recurrent Kawasaki disease as the most probable diagnosis.

The patient was treated with the standard medication regimen for Kawasaki disease (see discussion below) and subsequently had clinical improvement with treatment.

The patient was discharged three days after admission. Physical examination on the day of discharge was normal with the exception of mild, dry lips and mild desquamation of the genital area. The patient received a six-week prescrip- tion for aspirin therapy and her parent was asked to follow up with their primary care physician in one week and a pediatric cardiologist for a repeat echocardiogram several weeks later.

‌Discussion

As this case illustrates, recurrent Kawasaki disease was considered in this young child who presented with persistent fever (>102oF) of unknown origin for more than five days and had been diagnosed previously with Kawasaki disease in the last 12 months.5

This disease can cause dramatic effects on the cardio- vascular system if not identified and treated promptly and aggressively. Recurrent Kawasaki disease has an increased risk of causing coronary artery aneurysms, thrombosis, rup- ture, myocarditis, pericarditis, and myocardial damage, along with sudden death compared with the first presenta- tion of the disease.5

Kawasaki disease is a clinical diagnosis based on pre- sentation of persistent fever for at least five days and four of five of the following characteristics:

1. Polymorphous rash

2. Characteristic changes in extremities to include ery- thema or desquamation of genital area, fingers, or toes (Fig. 2)

3. Bilateral conjunctivitis

4. Cervical lymphadenopathy

5. Oropharyngeal changes including “strawberry” tongue or dry, erythematous, cracked lips (Fig. 3).5,6

‌Figure 3 Erythema and edema of the lips. (Reprinted with the permission from Dr. Jim Thomas at dermnet.com.)

This patient’s clinical presentation with a persistent fe- ver, edematous hands and feet, erythematous lips and oral mucosa, and desquamation of genitals supported the diag- nosis of Kawasaki disease. Because of the patient’s history of a previous diagnosis within the previous 12 months, the diagnosis of recurrent Kawasaki disease was made.

The diagnosis of Kawasaki disease has no definitive radiologic or laboratory test. The differential diagnosis would include aseptic or bacterial meningitis, scarlet fever, juvenile rheumatoid arthritis, drug reactions, and other in- fectious processes. Physicians should exclude these other disease processes as needed with a complete blood count, blood cultures, urine cultures, chest radiograph, or lumbar puncture based on clinical symptoms. Typical laboratory findings in Kawasaki disease include elevation of acute- phase reactants (ie, white blood count with left shift, eryth- rocyte sedimentation rate, C-reactive protein) with negative cultures. In this case, the clinical manifestations, nonspe- cific laboratory findings, and previous diagnosis of Kawa- saki disease all support suspicion for recurrent Kawasaki disease.

Once a diagnosis has been made, the patient should be treated using the standard medication regimen for Kawasaki disease that includes intravenous gamma globulin and oral aspirin. Standard treatment includes a single dose of intra- venous immunoglobulin (IVIG), 2 g/kg body weight over 12 hours, which has shown to reduce the incidence and severity of aneurysm formation and symptomatic relief for the acute illness.1 Although IVIG is not entirely without risk, its benefits outweigh the risks in patients with con- firmed Kawasaki disease. Aspirin is initially administered at high-dose intervals for two days at 80 –100 mg/kg body weight per day divided into four intervals. This dose is continued until the patient has been afebrile for 48 hours, and then the dose is decreased to 3–5 mg/kg per day for six to eight weeks for its antiinflammatory and antithrombotic effects.1 Aspirin may be continued indefinitely in patients who develop coronary abnormalities as a result of Kawasaki disease. Physicians need to inform the caregivers for these patients about the possible risk of Reyes syndrome if aspirin therapy is continued.

Current research states that baseline echocardiography and an electrocardiogram should be obtained one to two weeks after presentation of the disease and four to six weeks after the treatment phase to confirm that there is no damage to cardiac vasculature and cardiac muscle. Most anatomical

structural damage tends to occur one to two weeks after symptom onset. The ability to recognize the signs and symptoms of anatomical structure damage, such as the de- velopment of coronary artery aneurysms, is critical to pre- vent further morbidity of the disease process. Depending on the level of structural damage to the coronary arteries, it may be necessary to place the patient on physical activity restriction. At the minimum, the patient should undergo cardiovascular risk assessment and counseling at five-year intervals. This follow-up schedule would obviously need to be modified if the patient is in a higher risk group, and may include invasive cardiac testing. A pediatric cardiologist should be consulted to assess risk and provide further test- ing options as needed.

In summary, it is imperative to recognize the signs and symptoms of Kawasaki disease and be able to make the clinical diagnosis in a timely manner. Making this diag- nosis and providing treatment reduces the long term sequelae associated with the disease. It is also important to have an understanding of the effects of Kawasaki disease on the cardiac muscle and vasculature in clinical practice. The rare presentation of recurrent Kawasaki disease should remain in the differential diagnosis of a pediatric patient presenting with fevers, rash, and a pre- vious history of Kawasaki disease.

‌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 110:2747-2771, 2004‌

2. ‌Freeman AF, Shulman ST: Kawasaki disease: summary of the Ameri- can Heart Association guidelines. Am Fam Physician 74:1141-1148, 2006

3. ‌Hsieh YC, Wu MH, Wang JK, et al: Clinical features of atypical Kawasaki disease. J Microbiol Immuno Infect 35:57-60, 2002

4. ‌Gupta-Malhotra M, Rao PS: Current perspectives on Kawasaki’s dis- ease. Indian J Pediatr 72:621-629, 2005

5. Pemberton MN, Doughty IM, Middlehurst RM, et al: Recurrent Kawa- saki disease. Br Dent J 186:270-271, 1999

6. 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. Pediatrics 114:1708-1733, 2004