Abstract
This is a prospective study of a cohort of 70 children with Kawasaki disease (KD) admitted from April 2002 to April 2007 to a tertiary hospital in Brasilia, Brazil. Of the 70 children, only 32 (45.7%) were referred during the acute phase of the disease and only 15 (21.4%) were referred with the correct diagnosis. Coronary aneurysms were detected in 13 (18.5%). A high suspicion index is essential in order to detect new cases as KD is probably underdiagnosed in Brazil and other developing countries, and an early diagnosis will dramatically decrease its life-threatening complications.
Introduction
Kawasaki disease (KD) is an acute childhood multi-system vasculitis of unknown aetiology that occurs preferentially in children under five years of age, and is clinically characterized by the presence of ≥five days of fever and ≥four of five main clinical features (rash, non-purulent conjunctivitis, lip and oropharyngeal changes, non-suppurative cervical lymphadenopathy, and changes in the extremities). Coronary arteries are preferentially affected, and 20% to 25% of untreated children usually develop silent coronary artery aneurysms that may result in sudden death or myocardial infarction. KD aetiology remains elusive although the seasonal nature, the striking racial differences and the presence of significant immunoregulatory abnormalities support the existence of an infectious trigger leading to an immune-mediated reaction in genetically predisposed children. 1,2
Treatment with high-dose (2 g/g/day) of intravenous immunoglobulin (IVIG) in association with aspirin within the first 10 days after the onset of fever significantly reduces the risk of coronary-artery aneurysms. 3
Reports of KD from developing countries are rare. In an attempt to raise the awareness of the disease and to call attention to the importance of an early diagnosis of this potentially fatal disorder, the aim of the present study was to report a five-year experience in diagnosing and managing KD in the city of Brasília (Brazil).
Methods
This is a cohort prospective study of KD patients followed from April 2002 to April 2007. The protocol was approved by the Health Sciences Ethics Committee and was carried out at the Pediatric Rheumatology Unit of the Brasilia General Hospital. The KD diagnosis was established according to criteria of the American Heart Association. 2 The diagnostic work-up included the following investigations: complete blood count; platelet count; antiestreptolysin O (ASO) level; erythrocyte sedimentation rate (ERS); urea; and electrolytes. Echocardiography was performed with consent using an echo-Doppler apparatus (ALOKA SSD 2200, Japan). All patients were treated with IVIG at the time of their diagnosis.
Results
Seventy children (45 boys), with ages ranging from two months to 11 years (mean: 4.2; median: 3.2 years) fulfilled the KD diagnosis criteria. The disease peak frequency was observed in the two- to three-year age group (18 cases, 25.7%) (Figure 1).
Age distribution, in years, of 70 cases of Kawasaki disease
A seasonal variation in the disease incidence was observed with an increased number of cases occurring during the May-June and November-December periods. Only 15 (21.4%) of the 70 patients were referred with a correct KD diagnosis, the most frequent misdiagnosis being allergic reactions and viral infections. The main KD diagnosis criteria and the clinical features less frequently found among our patients are shown in Table 1.
Frequency of diagnostic criteria in 70 patients with Kawasaki disease
The results of routinely performed laboratory tests in all KD children in the acute phase were: increased number of leucocytes (>12×103/mm3) in 58 (82.8%); evidence of inflammatory activity (elevated ERS) in 58 (82.8%); antiestreptolysin O (ASO) above >200 UT in 15 (21.4%); thrombocytopenia (platelets <150.000) in five (7.14%); and anaemia with haemoglobin ≤10 mg/dL in 35 (50%). During the sub-acute phase, thrombocytosis (blood platelets >500,000) was observed in 54 patients (77.1%). Echocardiography, performed in all cases with consent, detected small left coronary aneurysms in 13 children (18.5%) and aortic aneurysm in one.
With consent, 69 patients received a single dose of 2 g/kg of IVIG, although only 32 (45.7%) received the dose during the first 10 days of the disease onset. In 28 patients, aspirin (80 mg/kg/day) was used as an anti-inflammatory drug during the acute phase and in 54 patients with thrombocytosis, as an anti-platelet agent (3–5 mg/kg/day).
Discussion
Although it has now been almost 40 years since the first description of this condition, its aetiology continues to be obscure; its diagnosis has been exclusively based on anamnesis and clinical signs or symptoms. KD has been reported worldwide, but it has rarely been described in developing countries. 4 It is not known how many cases, especially those symptomatically incomplete, remain undiagnosed during the acute phase evolving silently to calamitous heart conditions years later. The fact that the mean and median age of our group (4.2 and 3.2 years, respectively) is well above the median and mean age reported for other countries strongly suggest that we frequently miss the KD diagnosis, mainly during the first two years of life. 4–6 Another worrying fact is that only 18 (21.4%) of the referred children were appropriately diagnosed as KD by the primary physician, the most frequent misdiagnosis being allergic reactions and infectious diseases. Eleven children with coronary aneurysms were referred during the sub-acute phase, which suggest that even in cases in which KD was appropriately identified, it was probably a diagnosis made because of persisting fever and a lack of response to the proposed therapy. As the administration of IVIG within the first 10 days is crucial in preventing the appearance of coronary aneurysms 7,8 , this delayed diagnosis probably contributes to the high prevalence of cardiac sequels among our patients. Another fact that deserves attention is the sharp seasonal increase observed in our sample in November/December and May/June periods that, in our region, correspond to the beginning and end of the rainy season. Seasonal variations in the KD incidence have already been observed and, although the predominant season varies from country to country, the maximum number of cases has been recorded at the time of a change in weather. 9 It is still unknown whether the meteorological conditions themselves predispose to KD or if they alter the epidemiology of the aetiological agents. 10
KD is a serious paediatric disease, which presents significant diagnostic challenges. It is important to maintain a high degree of clinical awareness in order to identify new cases at the onset. An early clinical diagnosis is essential for the early provision of therapeutic measures and the transfer of the patient to a medical centre with sufficient resources for the diagnosis and treatment that will dramatically decrease the possibility of life-threatening complications.
The current prevalence of KD in developing countries is still unknown. The fact that it is probably underdiagnosed and misdiagnosed probably results in an increased prevalence of cardiac sequels.