|Year : 2013 | Volume
| Issue : 1 | Page : 35-39
Kawasaki disease: A university hospital experience
Amer A Lardhi
Department of Pediatrics, King Fahd Hospital of the University, Al Khobar, Kingdom of Saudi Arabia
|Date of Web Publication||3-Jun-2013|
Amer A Lardhi
PO Box 40051, Al-Khobar 31952
Kingdom of Saudi Arabia
Background: Kawasaki disease (KD) is an acute vasculitis of unknown etiology; it is the leading cause of acquired heart disease in children. KD is poorly understood in the Kingdom of Saudi Arabia (KSA).
Objective: To examine the epidemiological, clinical characteristics, and outcomes of KD in children diagnosed and treated at a tertiary care hospital in eastern province of the KSA.
Materials and Methods: A retrospective study of 35 patients admitted to the hospital with the diagnosis of KD was conducted at King Fahd Hospital of the University, Al-Khobar, KSA, from 1992 to 2012. Demographics, clinical features, laboratory findings, treatment, and patient outcome were analyzed.
Results: The incidence was 7.4 per 100,000 children under five. The male-to-female ratio was 1.9:1. The median age at diagnosis was 15 months, and the diagnosis was made after a mean of 8.1 days of fever. A seasonal peak during the winter-spring months was observed. Thirty-two patients (91%) had classical presentation of KD. Conjunctivitis, changes in the oropharynx, and a polymorphous rash were the most common manifestations. Cardiac involvement was detected in 51%, with coronary artery abnormalities (CAA) noted in 34%. Patients were treated with immunoglobulin and aspirin. The CAA regressed in all patients but one by 12 months. This one child still had persistent aneurysms at 2 years of follow-up.
Conclusion: The findings of this study showed that the basic clinical and epidemiological features associated with KD, in the KSA, were similar to those reported from regions in other parts of the world. A nationwide survey, however, is necessary to investigate the overall incidence, potential risk factors, and magnitude of KD disease in the KSA.
Keywords: Coronary aneurysm, Kawasaki disease, Saudi Arabia
|How to cite this article:|
Lardhi AA. Kawasaki disease: A university hospital experience. Saudi J Med Med Sci 2013;1:35-9
| Introduction|| |
Kawasaki disease (KD) is an acute multisystem vasculitis of the small and medium caliber vessels, with a striking predilection for the coronary arteries.  Since its original description by Tomisaku Kawasaki in 1967, KD has emerged as a leading cause of acquired heart disease in children. , KD is recognized worldwide among different ethnic groups. , Most patients are children below five years of age. Males slightly predominate by a ratio of 1.5-2:1.  Despite mounting evidence of the possible role of microbiological agents, the etiology of KD remains obscure. , The diagnosis of KD is based primarily on clinical criteria that correspond to clinical symptoms. , Early recognition of KD is crucial for patient management and the prevention of long-term sequelae. Treatment with intravenous immunoglobulin (IVIG) and aspirin reduces the risk of coronary artery abnormalities (CAA) when administered within 10 days of fever onset. , Although many studies have reported on this disease, studies from Saudi Arabia and the region are scarce. ,, In the current report, the epidemiology and clinical profile of 35 patients with KD, seen over a 20 year period at King Fahd Hospital of the University, Al-Khobar, in the eastern province of Saudi Arabia, are presented.
| Materials and Methods|| |
The medical records of all patients that had KD between October 1992 and September 2012 were retrieved and retrospectively analyzed. The diagnosis of KD was based on the diagnostic guidelines reported by the American Heart Association Committee on Rheumatic Fever, Endocarditis, and KD.  Fever persisting for at least 5 days and the presence of at least four of the following five principal features:
Incomplete KD was defined as: 
- Changes in extremities: Acute: Erythema or edema of hands or feet Convalescent: Desquamation of fingertips
- Polymorphous exanthem
- Bilateral, bulbar conjunctival injection without exudate
- Changes in lips and oral cavity: Erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosa
- Cervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral.
Fever lasting for at least 5 days and
The diagnosis of KD can be made on day four of illness in the presence of four or more criteria.  Demographic data (age at presentation, gender, and ethnicity), clinical features (symptoms at presentation, fever duration, comorbidity, treatment with IVIG, and aspirin), laboratory data (complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), liver function testing, urine analysis, cerebrospinal fluid (CSF) analysis, and abdominal ultrasound) were collected and reviewed. Twelve lead electrocardiogram (EKG) and two-dimensional echocardiography were performed for evaluation of the structures and the function of the heart in all children on presentation, 2 weeks after the diagnosis and thereafter depending on the initial findings. Continuous variables (such as age) were expressed as the mean, median, and range. Absolute numbers as well as percentages are presented for the study variables. As this is a descriptive study, no statistical tests of significance were used.
- At least two of the five clinical criteria for KD
- Absence of any other reasonable explanation for the illness
- Laboratory findings consistent with severe systemic inflammation.
| Results|| |
During the study period, the total number of children (12 years old) admitted to the pediatric ward was 24,402. Thirty-five patients were diagnosed with KD, for an incidence of 7.4/100,000 children younger than 5 years of age. As to ethnicity, 25 (71.4%) patients were of Saudi descent, 7 (20%) Middle Eastern, and 3 (8.6%) Asian. There were 23 males and 12 females, with a male to female ratio of 1.9:1. The mean age at diagnosis was 25.5 months and the median was 15 months (range 6 weeks to 8 years). Twelve (34.3%) children were diagnosed at less than 1 year of age, and 31 (89%) at less than 5 years of age. The disease occurred during the winter season in 16 cases (45.8%), spring in 12 (34.3%), summer in 4 (11.4%), and fall in 3 (8.5%) [Table 1]. The diagnostic criteria for KD were fulfilled in 32 (91.4%) patients. Only three (8.6%) cases were diagnosed with incomplete criteria (two patients with a positive echocardiogram and one after exclusion of other possible diagnoses). Five (14%) patients with four or more criteria were diagnosed at 4 days of fever. The mean duration of fever was 8.1 days (range 4-21), with five (14%) patients having fever for less than 5 days and eight (23%) patients having fever for more than 10 days, at diagnosis. The frequency of KD criteria among the patients is as follows [Table 2]: Conjunctivitis and oropharyngeal changes 91.4% each, skin rash 83%, cervical lymphadenopathy 71%, and changes noted in the peripheral extremities 66%. The associated clinical features included irritability, arthralgia, gastrointestinal symptoms, jaundice, anemia, perineal desquamation, hydrops of the gallbladder, and aseptic meningitis [Table 2].
|Table 1: Demographic and epidemiological data of 35 patients with Kawasaki disease|
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The Laboratory data are summarized in [Table 3]. Anemia for age was detected in 66% of cases, leukocytosis in 63% and thrombocytosis (either on presentation, or toward the end of the second week of the illness) in 86%. All cases except two had an increased ESR (range 16 to 152 mm 1 st hour); similarly, all but one had increased CRP levels. Elevated serum transaminases were found in 28% of cases, a reduced albumin level in 80%, and increased serum bilirubin level in 24%. The CSF was analyzed in 7/35 cases and pleocytosis was detected in 4 of them. Abdominal ultrasound was performed in 18/35 children. Only one of these patients had hydrops of the gallbladder. The EKG showed sinus tachycardia in 17/35 (49%) patients, a depressed ST segment in 1, and reduced QRS voltage in 1 child. Cardiac involvement was found in 18/35 (51%) children (12 males and 6 females). CAA were detected in 12/35 (34%) patients, 6 had ectasia, and 6 had aneurysms. The right coronary artery was involved in four patients, in two the left coronary artery was involved, and in six patients, both the right and the left coronary arteries were involved. The aneurysms varied in size; four patients had small aneurysms (<5 mm) and two had moderate sized aneurysms (<8 mm). A minimal to moderate pericardial effusion was seen in nine cases and valvular regurgitation (mitral and tricuspid valve) in five. Left ventricular function was within normal limits in all cases [Table 4]. Regression of the coronary lesions was observed in all but one at 12 months of follow up. This patient had persistent coronary artery aneurysms at 2 years of follow up. All other cardiac abnormalities have resolved completely on follow-up. Aspirin (80-100 mg/kg/day) was given to all children during the acute phase, followed by 3-5 mg/kg/day for patients with CAA. IVIG (2 g/kg over 12 hours or 400 mg/kg/for five consecutive days) was administered in all cases. Sixty-nine percent of the cases received IVIG within 10 days of the onset of fever. The rest of the patients (31%) received IVIG after the 10 th day of illness. Two patients, that had persistent fever 48 hours after the initial IVIG dose, received a second dose.
| Discussion|| |
KD in an eastern province of Saudi Arabia is primarily a disorder affecting pre-school children. The incidence was 7.4 per 100,000 children under 5 years of age in this study; this is comparable to the rate previously reported from the region and from other countries. ,, However, the incidence was lower than that reported from far eastern countries. , The worldwide annual incidence of KD derived from a nationwide epidemiological survey and from analysis of hospital based data varies widely from 3.4 to 218.6/100,000 children less than 5 years of age.  The true incidence in most Middle Eastern countries is not known. The recently published data from Jordan reported an incidence rate of 0.09%.  The age distribution and male preponderance observed in this study is consistent with other reports from the region and various parts of the world. ,, The disease occurred throughout the year, with seasonal clustering observed during the winter and spring months. This finding is consistent with the results of other major epidemiological studies conducted in different countries. ,
The diagnosis of KD is based on well-established clinical criteria. In this review, 32 (91%) children had classic disease and only 3 had incomplete disease. It has been postulated that children with incomplete disease are at higher risk of developing CAA than those with classical presentations.  Thus, KD should be part of the differential diagnosis, particularly in younger children with fever and less than four criteria that have suggestive laboratory findings such as an increased white blood cell count (WBC), ESR, CRP, or thrombocytosis after 7 days of fever.  In this study, the mean duration of fever at diagnosis was 8.1 days. Seventy-eight percent of the cases had been diagnosed within 10 days after the onset of fever. Although this finding may suggest a better awareness of KD, among health care workers, over one-quarter of the patients had their disease diagnosed after 10 days of fever. Delay in the diagnosis and management of KD carries a significant risk for developing CAA.  Anderson et al noted that delayed diagnosis was not significantly related to healthcare system factors but was related to the dispersion over time of the development of clinical features. 
The clinical findings essential for the diagnosis of KD together with the associated clinical and laboratory findings were used for the diagnosis of KD in all patients. The frequency of the principal clinical criteria observed in this study was in accordance with the results of other studies. ,, Bilateral conjunctival injection and changes in the oral cavity and lips were the most commonly detected clinical signs, while cervical lymphadenopathy and changes in the peripheral extremities were the least common of the principal clinical features observed.
Cardiac involvement is the most important feature of KD; it has been variably reported in up to 50% of cases.  In untreated KD, 20-40% of patients develop CAA. , Timely treatment with IVIG, however, decreases the incidence of coronary artery disease to less than 5%. , Among the children in the current series, 18/35 (51%) had cardiac involvement. Pericardial effusion occurred in 8 (22%) cases. The effusion was minimal and transient in most. One patient (a 5 year old girl), developed a significant pericardial and pleural effusion, respiratory distress, and hypotension. She required pericardiocentesis and respiratory support, before she made a full recovery.
Another non-coronary cardiac involvement was valvular regurgitation, which was observed in 14% of cases. The mitral and tricuspid valves were affected in three patients and the mitral valve alone in two; the regurgitation was mild and resolved within a few months of follow up. This is consistent with studies reported previously. , In the current study, the incidence of CAA was high, with 12 patients (37%) developing coronary changes despite treatment with IVIG. This might be explained by a delay of recognition of the disease, and hence a delay in starting treatment. As well as a younger age, since 50% of these groups were infants, and less than 1 year of age. A young age (age < 1 year), male gender, and prolonged fever are known risk factors for developing coronary abnormalities, which may precipitate thrombosis or evolve into segmental stenosis during the chronic phase of disease. , Coronary artery involvement regressed in all patients but one by 12 months. This patient had persistent coronary lesions at 2 years of follow-up. Small and medium sized aneurysms are known to have a greater likelihood of regression. 
| Conclusion|| |
The findings of this study document the incidence of Kawasaki disease in this region of the KSA and confirm the clinical similarities with various reports from other parts of the world. Early diagnosis and prompt treatment are crucial in preventing serious complications. A prospective study at the national level is necessary to investigate the overall incidence and magnitude of Kawasaki disease in the Kingdom of Saudi Arabia.
| References|| |
|1.||Scuccimarri R. Kawasaki syndrome. Pediatr Clin North Am 2012;59:425-45. |
|2.||Kawasaki T, Kosaki F, Okawa S, Shigemitsu I, Yanagawa H. A new infantile acute febrile mucocutaneous lymph node syndrome (MLNS) prevailing in Japan. Pediatrics 1974;54:271-6. |
|3.||Burns JC. Kawasaki Disease update. Indian J Pediatr 2009;76:71-6. |
|4.||Nakamura Y, Yanagawa H. The worldwide epidemiology of Kawasaki disease. Prog Pediatr Cardiol 2004;19:99-108. |
|5.||McCrindle BW, Li JS, Minich LL, Colan SD, Atz AM, Takahashi M, et al. Coronary artery involvement in children with Kawasaki disease: Risk factors from analysis of serial normalized measurements. Circulation 2007;116:174-9. |
|6.||Lin YT, Manlhiot C, Ching JC, Han RK, Nield LE, Dillenburg R, et al. Repeated systematic surveillance of Kawasaki disease in Ontario from 1995 to 2006. Pediatr Int 2010;52:699-706. |
|7.||Newburger JW, Fulton DR. Kawasaki disease. Curr Opin Pediatr 2004;16:508-14. |
|8.||Newburger JW, Takahashi M, Gerber M, Gewitz MH, Tani LY, Burns JC, 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;110:2747-71. |
|9.||Dajani AS, Taubert KA, Gerber MA, Shulman ST, Ferrieri P, Freed M, et al. Diagnosis and therapy of Kawasaki disease in children. Circulation 1993;87:1776-80. |
|10.||Nakamura Y, Yashiro M, Uehara R, Sadakane A, Chihara I, Aoyama Y, et al. Epidemiologic features of Kawasaki disease in Japan: results of the 2007-2008 nationwide survey. J Epidemiol 2010;20:302-7. |
|11.||Al-Harbi KM. Kawasaki disease in Western Saudi Arabia. Saudi Med J 2010;31:1217-20. |
|12.||Ghazal SS, Alhowasi M, El Samady MM. Kawasaki Disease in a Paediatric Hospital in Riyadh. Ann Trop Paediatr 1998;18:295-9 |
|13.||Saffar MJ, Reshidighager F. Kawasaki Disease in East Mazandaran, Islamic Republic of Iran, 1997-2002. East Mediterr Health J 2005;11:28-35. |
|14.||Schiller B, Fasth A, Bjorkhem G, Elinder G. Kawasaki disease in Sweden: Incidence and clinical features. Acta Paediatr 1995;84:769-74. |
|15.||Harnden A, Mayon-White R, Sharma R, Yeates D, Goldacre M, Burgner D. Kawasaki disease in England: Ethnicity, deprivation, and respiratory pathogens. Pediatr Infect Dis J 2009;28:21-4. |
|16.||Park YW, Han JW, Hong YM, Ma JS, Cha SH, Kwon TC, et al. Epidemiologic features of Kawasaki disease in Korea, 2006-2008. Pediatr Int 2011;53:36-9. |
|17.||Uehara R, Belay ED. Epidemiology of Kawasaki Disease in Asia, Europe, and the United States. J Epidemiol 2012;22:79-85. |
|18.||Al-Ammouri I, Al-Wahsh S, Khuri-Bulos N. Kawasaki disease in Jordan: Demographics, presentation, and outcome. Cardiol Young 2012;22:390-5. |
|19.||Hassan B, Kalis NN. Early compared to late presentation of Kawasaki Disease. Bahrain Med Bull 2010;32:15-7. |
|20.||Asadi-Pooya AA, Borzoee M, Amoozgar H. The experience with 113 patients with Kawasaki disease in Fars Province, Iran. Turk J Pediatr 2006;48:109-14. |
|21.||Alexopoulos A, Vekiou A, Lycopoulou L, Tavena A, Lagona E, Kakourou T. Kawasaki disease in Greek children: A retrospective study. J Eur Acad Dermatol Venereol 2013;27:580-8. |
|22.||Bronstein DE, Dille AN, Austin JP, Williams CM, Palinkas LA, Burns JC. Relationship of climate, ethnicity, and socioeconomic status to Kawasaki disease in San Diego County, 1994-1998. Pediatr Infect Dis J 2000;19:1087-91. |
|23.||Nakamura Y, Yanagawa H. The worldwide epidemiology of Kawasaki disease. Prog Pediatr Cardiol 2004;19:99-108. |
|24.||Sonobe T, Kiyosawa N, Tsuchiya K, Aso S, Imada Y, Imai Y, et al. Prevalence of coronary artery abnormality in incomplete Kawasaki disease. Pediatr Int 2007;49:421-6. |
|25.||Singh-Grewal D, Wong M, Isaacs D. Diagnosis, treatment and outcome of Kawasaki disease in an Australian tertiary setting: A review of three years experience. J Paediatr Child Health 2005;41:495-9. |
|26.||Sittiwangkul R, Pongprot Y, Silvilairat S, Phornphutkul C. Delayed diagnosis of Kawasaki disease: Risk factors and outcome of treatment. Ann Trop Paediatr 2011;31:109-14. |
|27.||Anderson MS, Todd JK, Glode MP. Delayed diagnosis of Kawasaki syndrome: An analysis of the problem. Pediatrics 2005;115:e428-33. |
|28.||Hashemian H, Karambin MM. Kawasaki Disease: An epidemiological and clinical study. Acta Med Iran 2009;47:455-7. |
|29.||Yun SH, Yang NR, Park S. Associated Symptoms of Kawasaki Disease. Korean Circ J 2011;41:394-8. |
|30.||Harnden A, Takahashi M, Burgner D. Kawasaki disease. BMJ 2009;338:b1514. |
|31.||Akhtar S, Alam MM, Ahmed MA. Cardiac involvement in Kawasaki disease in Pakistani children. Ann Pedaitr Cardiol 2012;5:129-32. |
|32.||Royle J, Burgner D, Curtis N. The diagnosis and management of Kawasaki disease. J Paediatr Child Health 2005;41:87-93. |
|33.||Newburger JW, Takahashi M, Beiser AS, Burns JC, Bastian J, Chung KJ, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 1991;324:1633-9. |
|34.||Nakano H, Saito A, Ueda K, Tsuchitani Y. Valvular lesions complicating Kawasaki disease: Doppler echocardiographic evaluation. J Cardiogr 1986;16:363-71. |
|35.||Song D, Yeo Y, Ha K, Jang G, Lee J, Lee K, et al. Risk factors for Kawasaki disease-associated coronary abnormalities differ depending on age. Eur J Pediatr 2009;168:1315-21. |
|36.||Belay ED, Maddox RA, Holman RC, Curns AT, Ballah K, Schonberger LB. Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003. Pediatr Infect Dis J 2006;25:245-9. |
|37.||Takahashi M, Mason W, Lewis AB. Regression of coronary aneurysms in patients with Kawasaki syndrome. Circulation 1987;75:87-94. |
[Table 1], [Table 2], [Table 3], [Table 4]