Kawasaki disease (KD) is an acute, systemic vasculitis of unknown etiology that occurs predominantly in infants and young children less than 5 years old. It was firstly reported by Kawasaki in 1967¹⁾, and has subsequently been reported worldwide in children of all races. A delayed diagnosis of KD, especially incomplete Kawasaki disease (IKD)²⁾; which has persistent fever with fewer than four other principal clinical features of KD, can lead to the development of coronary artery lesions (CALs). Recently, the diagnosis of IKD has been increasing, and the reported prevalence was 15% to 36.2% among patients with KD^3,4,5,6,7,8), making it difficult for pediatrician to diagnose KD. Therefore, additional clues that are helpful in the diagnosis of IKD are needed for the early detection and treatment of IKD. Suggested clues are erythema and induration of a previous Bacille Calmette-Guerin inoculation site^9,10), anterior uveitis (AU)¹¹⁾, elevated serum levels of alanine aminotransferase (ALT)¹²⁾, brain natriuretic peptide (BNP)¹³⁾ and N-terminal pro-BNP^14,15), hyponatremia¹⁶⁾, echocardiographic abnormalities other than CALs¹⁷⁾ (pericardial effusion, dysfunction of the left ventricle, mitral regurgitation). AU is a common finding in the early stage of KD, so a slit lamp examination may be a helpful in the early detection of patients with IKD. No study has examined the usefulness of AU for the early recognition and treatment of IKD in Korea. Therefore, we retrospectively investigated the diagnostic value of AU for the early detection of IKD.

During the study period, 111 patients were diagnosed having IKD at Uijeongbu St. Mary's Hospital. Of these, 41 had AU on admission (group 1), and 70 did not have AU (group 2). The demographic data of each group are summarized in Table 1. The mean age was significantly older in group 1 than in groups 2 (46.5±19.93 months vs. 29.8±21.28 months, P<0.001). This data might mean that there could be some patients with AU in the group 2, because the very young aged patients might not get the correct diagnosis of AU due to the lack of cooperation during slit lamp examination. Males predominated (67 of 111, 60.3%) as like as the patients with complete KD and the male-to-female ratio was 1.5:1. The duration of fever before the first IVIG was not significantly different between the 2 groups (P=0.533). There was no significant difference in the number of diagnostic criteria between 2 groups (Table 2), and all of the enrolled patients had desquamation of finger tips and thrombocytosis in the subacute phase of KD, confirming the final diagnosis of KD. The rates of additional IVIG treatment did not significantly differ between the two groups. The necessity of second-line therapy, such as systemic corticosteroid or infliximab, was significantly higher in group 2 than in group 1. Group 2 had a significantly longer duration of hospitalization than group 1. The laboratory results on admission did not differ significantly between the two groups (Table 3). CA dilatation was observed in 3 patients in group 1 (1.7%), 19 patients in group 2 (27.1%), and the rate of dilatation was significantly higher in group 2 than in group 1 (Table 4) (P=0.008). The only 1 patient in group 2 (1.4%), who received infliximab, developed giant coronary aneurysm. The fact that group 1 had lower risk of CALs than group 2 seemed to demonstrate that the detection of AU could lead to earlier diagnosis and treatment of patients with IKD before they develop CALs (relative risk [RR], 1.298; 95% confidential interval, 10.93–1.540).

Kawasaki disease is the most common acquired heart disease in children. Delayed treatment can cause cardiac complications, including CA dilatation and aneurysm, myocardial infarction, pericardial effusion, valvular regurgitation. KD is diagnosed using the diagnostic criteria^12,18) based on the clinical symptoms and laboratory findings, because there is no specific diagnostic test. Ophthalmologic manifestations of KD have been described since 1981¹⁹⁾, mostly nonexudative bulbar conjunctivitis and uveitis¹²⁾. Superficial punctate keratitis, vitreous opacity, choroidal and retinal changes, papilledema, subconjunctival hemorrhage, and macular edema are less common²⁰⁾. Some studies have included AU as an additional diagnostic tool that can be helpful for the early recognition and treatment of IKD^21,22,23) and the prevention of CALs. The patients with IKD younger than 6 months of age, or older than 5 years of age, have higher possibility of developing CA complications due to late diagnosis and treatment^3,5). Uveitis can be classified anatomically, with AU accounting for 30%–40%, posterior uveitis accounting for 40%–50%, intermediate uveitis accounting for 10%–20%, and diffuse uveitis accounting for 5%–10%²⁴⁾. The most common cause²⁴⁾ of AU in children is juvenile idiopathic arthritis, while other diseases can be associated with AU including KD, retinoblastoma, leukemia, juvenile xanthogranuloma, Coat's disease, retinitis pigmentosa, herpes virus infection, sarcoidosis, and retained intraocular foreign bodies following trauma. CALs were significantly less common in group 1 than group 2 (7.3% vs. 28.5%, P=0.008). Therefore, if a patient has an unexplained persistent fever and IKD is suspected, an ophthalmic examination is needed to identify the presence of AU. Korea has the second highest incidence rate of KD in the world. However, we do not have our own diagnostic criteria for KD and should establish Korean diagnostic guidelines of the disease with additional criteria such as AU for the early diagnosis of IKD and prevention of CA complications. To do this, it is necessary to objectively assess whether the detection of AU can help to diagnose and reduce the occurrence of CALs by preventing treatment delay through the triennial nationwide epidemiological survey in Korea. This study is the first such study in Korea, but it has some limitations. First, all of the patients with KD were not included, and only those with suspected IKD underwent ophthalmologic examinations. Second, the study had a small sample size because it was conducted at a single institute. Finally, the study was not a nationwide prospective study. We are planning a more objective, systematic study on IKD. We recommend that all patients with KD should be consulted to an ophthalmologist to determine the presence of AU. We think that AU may be recognized as one of the essential diagnostic criteria of KD, and the presence of AU may lead to the early diagnosis and treatment of IKD, reducing the occurrence of CALs. In conclusion, we recommend that pediatricians should consider AU as an important finding and cooperate with ophthalmologists when managing patients with suspected IKD.